Viruses

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13 pages, 1759 KiB

Open AccessArticle

Deep Sequencing Data and Infectivity Assays Indicate that Chickpea Chlorotic Dwarf Virus is the Etiological Agent of the “Hard Fruit Syndrome” of Watermelon

by Takoua Zaagueri^1,2

, Laura Miozzi²

, Monia Mnari-Hattab¹

, Emanuela Noris²

, Gian Paolo Accotto²

and Anna Maria Vaira^2,*

¹ Laboratoire de Biotechnologie Appliquée à l’Agriculture, Institut National de la Recherche Agronomique de Tunisie (INRAT), Université de Carthage, El Rue Hedi Karray Menzah, 1004 Tunis, Tunisia

² Institute for Sustainable Plant Protection (IPSP), CNR, 10135 Turin, Italy

Viruses 2017, 9(11), 311; https://doi.org/10.3390/v9110311 - 25 Oct 2017

Cited by 16 | Viewed by 6831

Abstract

Chickpea chlorotic dwarf virus (CpCDV), a polyphagous mastrevirus, family Geminiviridae, has been recently linked to the onset of the “hard fruit syndrome” of watermelon, first described in Tunisia, that makes fruits unmarketable due to the presence of white hard portions in the [...] Read more.

Chickpea chlorotic dwarf virus (CpCDV), a polyphagous mastrevirus, family Geminiviridae, has been recently linked to the onset of the “hard fruit syndrome” of watermelon, first described in Tunisia, that makes fruits unmarketable due to the presence of white hard portions in the flesh, chlorotic mottling on the rind, and an unpleasant taste. To investigate the etiological agent of this disease, total RNA extracted from symptomatic watermelon fruits was subjected to small RNA sequencing through next generation sequencing (NGS) techniques. Data obtained showed the presence of CpCDV and two other viral species. However, following validation through polymerase chain reaction (PCR), CpCDV was the only viral species consistently detected in all samples. Watermelon seedlings were then challenged by an agroinfectious CpCDV clone; several plants proved to be CpCDV-infected, and were able to produce fruits. CpCDV infected and replicated in watermelon fruits and leaves, leading to abnormality in fruits and in seed production, similar to those described in field. These results indicate that CpCDV is the etiological agent of the “hard fruit syndrome” of watermelon. Full article

(This article belongs to the Special Issue Geminiviruses)

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16 pages, 5814 KiB

Open AccessArticle

Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy against PEDV

by Xiaona Wang^1,†, Li Wang^1,†, Xuewei Huang¹, Sunting Ma¹, Meiling Yu¹, Wen Shi², Xinyuan Qiao^1,3, Lijie Tang^1,3, Yigang Xu^1,3,* and Yijing Li^1,3,*

¹ College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China

² College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China

³ Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Harbin 150030, China

^† These authors contributed equally to this work.

Viruses 2017, 9(11), 312; https://doi.org/10.3390/v9110312 - 25 Oct 2017

Cited by 71 | Viewed by 8654

Abstract

Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is [...] Read more.

Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is reported as a promising approach for inducing protective immunity against PEDV invasion. Furthermore, dendritic cells (DCs), professional antigen-presenting cells, link humoral and cellular immune responses for homeostasis of the intestinal immune environment. In this study, in order to explore an efficient oral vaccine against PEDV infection, a mucosal DC-targeting oral vaccine was developed using Lactobacillus casei to deliver the DC-targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE) antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in vivo. Significant differences (p < 0.05) in the immune response levels were observed between probiotics expressing the COE-DCpep fusion protein and COE antigen alone, suggesting better immune efficiency of the probiotics vaccine expressing the DC-targeting peptide fused with PEDV COE antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances vaccine antigen delivery efficiency, providing a useful strategy to induce efficient immune responses against PEDV infection. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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14 pages, 4201 KiB

Open AccessArticle

ABC Assay: Method Development and Application to Quantify the Role of Three DWV Master Variants in Overwinter Colony Losses of European Honey Bees

by Jessica L. Kevill¹, Andrea Highfield², Gideon J. Mordecai^2,3

, Stephen J. Martin¹

and Declan C. Schroeder^2,4,5,*

¹ School of Environment and Life Sciences, The University of Salford, Manchester M5 4WT, UK

² Viral Ecology, Marine Biological Association, Plymouth PL1 2PB, UK

³ Department of Earth, Ocean and Atmospheric Sciences and Biodiversity Research Centre, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada

⁴ School of Biological Sciences, University of Reading, Reading RG6 6LA, UK

⁵ Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA

Viruses 2017, 9(11), 314; https://doi.org/10.3390/v9110314 - 27 Oct 2017

Cited by 78 | Viewed by 8708

Abstract

Deformed wing virus (DWV) is one of the most prevalent honey bee viral pathogens in the world. Typical of many RNA viruses, DWV is a quasi-species, which is comprised of a large number of different variants, currently consisting of three master variants: Type [...] Read more.

Deformed wing virus (DWV) is one of the most prevalent honey bee viral pathogens in the world. Typical of many RNA viruses, DWV is a quasi-species, which is comprised of a large number of different variants, currently consisting of three master variants: Type A, B, and C. Little is known about the impact of each variant or combinations of variants upon the biology of individual hosts. Therefore, we have developed a new set of master variant-specific DWV primers and a set of standards that allow for the quantification of each of the master variants. Competitive reverse transcriptase polymerase chain reaction (RT-PCR) experimental design confirms that each new DWV primer set is specific to the retrospective master variant. The sensitivity of the ABC assay is dependent on whether DNA or RNA is used as the template and whether other master variants are present in the sample. Comparison of the overall proportions of each master variant within a sample of known diversity, as confirmed by next-generation sequence (NGS) data, validates the efficiency of the ABC assay. The ABC assay was used on archived material from a Devon overwintering colony loss (OCL) 2006–2007 study; further implicating DWV type A and, for the first time, possibly C in the untimely collapse of honey bee colonies. Moreover, in this study DWV type B was not associated with OCL. The use of the ABC assay will allow researchers to quickly and cost effectively pre-screen for the presence of DWV master variants in honey bees. Full article

(This article belongs to the Special Issue Antiviral Defense in Invertebrates)

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19 pages, 5027 KiB

Open AccessArticle

Differential Effect of Newly Isolated Phages Belonging to PB1-Like, phiKZ-Like and LUZ24-Like Viruses against Multi-Drug Resistant Pseudomonas aeruginosa under Varying Growth Conditions

by Simone Latz¹, Alex Krüttgen¹, Helga Häfner², Eva Miriam Buhl³

, Klaus Ritter¹ and Hans-Peter Horz^1,*

¹ Institute of Medical Microbiology, RWTH Aachen University Hospital, 52074 Aachen, Germany

² Department of Infection Control and Infectious Diseases, RWTH Aachen University Hospital, 52074 Aachen, Germany

³ Electron Microscopy Facility, RWTH Aachen University Hospital, 52074 Aachen, Germany

Viruses 2017, 9(11), 315; https://doi.org/10.3390/v9110315 - 27 Oct 2017

Cited by 53 | Viewed by 7602

Abstract

In this study, we characterize three phages (SL1 SL2, and SL4), isolated from hospital sewage with lytic activity against clinical isolates of multi-drug resistant Pseudomonas aeruginosa (MDR-PA). The host spectrum ranged from 41% to 54%, with all three phages together covering 79% of [...] Read more.

In this study, we characterize three phages (SL1 SL2, and SL4), isolated from hospital sewage with lytic activity against clinical isolates of multi-drug resistant Pseudomonas aeruginosa (MDR-PA). The host spectrum ranged from 41% to 54%, with all three phages together covering 79% of all tested clinical isolates. Genome analysis revealed that SL1 (65,849 bp, 91 open reading frames ORFs) belongs to PB1-like viruses, SL2 (279,696 bp, 354 ORFs) to phiKZ-like viruses and SL4 (44,194 bp, 65 ORFs) to LUZ24-like viruses. Planktonic cells of four of five selected MDR-PA strains were suppressed by at least one phage with multiplicities of infection (MOIs) ranging from 1 to 10⁻⁶ for 16 h without apparent regrowth of bacterial populations. While SL2 was most potent in suppressing planktonic cultures the strongest anti-biofilm activity was observed with SL4. Phages were able to rescue bacteria-infected wax moth larvae (Galleria melonella) for 24 h, whereby highest survival rates (90%) were observed with SL1. Except for the biofilm experiments, the effect of a cocktail with all three phages was comparable to the action of the best phage alone; hence, there are no synergistic but also no antagonistic effects among phages. The use of a cocktail with these phages is therefore expedient for increasing host range and minimizing the development of phage resistance. Full article

(This article belongs to the Section Bacterial Viruses)

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13 pages, 3144 KiB

Open AccessArticle

Antibody Cross-Reactivity between Porcine Cytomegalovirus (PCMV) and Human Herpesvirus-6 (HHV-6)

by Uwe Fiebig¹, Angela Holzer², Daniel Ivanusic¹, Elena Plotzki¹, Hartmut Hengel³

, Frank Neipel² and Joachim Denner^1,*

¹ Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany

² Institute of Virology, University Erlangen, Schlossgarten 4, 91054 Erlangen, Germany

³ Institute of Virology, Medical Center, Faculty of Medicine, University of Freiburg, Hermann-Herder-Strasse 11, 79104 Freiburg, Germany

Viruses 2017, 9(11), 317; https://doi.org/10.3390/v9110317 - 28 Oct 2017

Cited by 22 | Viewed by 5887

Abstract

Porcine cytomegalovirus (PCMV) infection is widely prevalent among pigs, and PCMV is one of the viruses which may be transmitted during xenotransplantation using pig cells, tissues, or organs. While human cytomegalovirus (HCMV) is a major risk factor for allotransplantation, it is still unclear [...] Read more.

Porcine cytomegalovirus (PCMV) infection is widely prevalent among pigs, and PCMV is one of the viruses which may be transmitted during xenotransplantation using pig cells, tissues, or organs. While human cytomegalovirus (HCMV) is a major risk factor for allotransplantation, it is still unclear whether PCMV is able to infect human cells or pose a risk for xenotransplantation. Previously, it was shown that transmission of PCMV after pig kidney to non-human primate transplantations resulted in a significantly reduced survival time of the transplanted organ. To detect PCMV, PCR-based and immunological methods were used. Screening of pigs by Western blot analyses using recombinant viral proteins revealed up to 100% of the tested animals to be infected. When the same method was applied to screen human sera for PCMV-reactive antibodies, positive Western blot results were obtained in butchers and workers in the meat industry as well as in normal blood donors. To exclude an infection of humans with PCMV, the sera were further investigated. PCMV is closely related to human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7), and a sequence alignment of glycoprotein B suggests that the antibodies may cross-react with identical epitope sequences. HCMV is not related with PCMV, and no correlation between antibody reactivity against PCMV and HCMV was detected. These data indicate that antibodies against PCMV found in humans are cross-reactive antibodies against HHV-6. Full article

(This article belongs to the Section Animal Viruses)

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15 pages, 2963 KiB

Open AccessArticle

Development of a Lethal Intranasal Exposure Model of Ebola Virus in the Cynomolgus Macaque

by Kendra J. Alfson¹, Laura E. Avena^1,2, Gabriella Worwa¹, Ricardo Carrion¹ and Anthony Griffiths^1,2,*

¹ Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX 78227, USA

² Graduate School of Biomedical Sciences, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA

Viruses 2017, 9(11), 319; https://doi.org/10.3390/v9110319 - 29 Oct 2017

Cited by 25 | Viewed by 6446

Abstract

Ebola virus (EBOV) is a filovirus that can cause Ebola virus disease (EVD). No approved vaccines or therapies exist for filovirus infections, despite an urgent need. The development and testing of effective countermeasures against EBOV requires use of animal models and a thorough [...] Read more.

Ebola virus (EBOV) is a filovirus that can cause Ebola virus disease (EVD). No approved vaccines or therapies exist for filovirus infections, despite an urgent need. The development and testing of effective countermeasures against EBOV requires use of animal models and a thorough understanding of how the model aligns with EVD in humans. The majority of published studies report outcomes of parenteral exposures for emulating needle stick transmission. However, based on data from EVD outbreaks, close contact exposures to infected bodily fluid seems to be one of the primary routes of EBOV transmission. Thus, further work is needed to develop models that represent mucosal exposure. To characterize the outcome of mucosal exposure to EBOV, cynomolgus macaques were exposed to EBOV via intranasal (IN) route using the LMA^® mucosal atomization device (LMA^® MAD). For comparison, four non-human primates (NHPs) were exposed to EBOV via intramuscular (IM) route. This IN exposure model was uniformly lethal and correlated with a statistically significant delay in time to death when compared to exposure via the IM route. This more closely reflects the timeframes observed in human infections. An IN model of exposure offers an attractive alternative to other models as it can offer insight into the consequences of exposure via a mucosal surface and allows for screening countermeasures via a different exposure route. Full article

(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)

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19 pages, 13186 KiB

Open AccessArticle

Atomic Resolution Structure of the Oncolytic Parvovirus LuIII by Electron Microscopy and 3D Image Reconstruction

by Nikéa Pittman^1,2

, Adam Misseldine^1,2, Lorena Geilen^1,2, Sujata Halder^1,2,†, J. Kennon Smith^1,2, Justin Kurian^1,2, Paul Chipman^1,2

, Mandy Janssen^3,‡, Robert Mckenna^1,2, Timothy S. Baker³, Anthony D’Abramo Jr.⁴, Susan Cotmore⁴, Peter Tattersall^4,5 and Mavis Agbandje-McKenna^1,2,*

¹ Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32611, USA

² Center for Structural Biology, The McKnight Brain Institute, University of Florida, Gainesville, FL 32611, USA

³ Department of Chemistry and Biochemistry and Division of Biological Sciences, University of California-San Diego, San Diego, CA 92093, USA

⁴ Department of Laboratory Medicine, Yale University Medical School, New Haven, CT 06520, USA

⁵ Department of Genetics, Yale University Medical School, New Haven, CT 06510, USA

^† Current address: Zydus Research Centre, Biotech Division, Cadila Healthcare Ltd., The Zydus Group, Ahmedabad, Gujarat 380015, India.

^‡ Current address: NanoImaging Services, Inc., 4940 Carroll Canyon Road, Suite 115, San Diego, CA 92121, USA.

Viruses 2017, 9(11), 321; https://doi.org/10.3390/v9110321 - 30 Oct 2017

Cited by 7 | Viewed by 8580

Abstract

LuIII, a protoparvovirus pathogenic to rodents, replicates in human mitotic cells, making it applicable for use to kill cancer cells. This virus group includes H-1 parvovirus (H-1PV) and minute virus of mice (MVM). However, LuIII displays enhanced oncolysis compared to H-1PV and MVM, [...] Read more.

LuIII, a protoparvovirus pathogenic to rodents, replicates in human mitotic cells, making it applicable for use to kill cancer cells. This virus group includes H-1 parvovirus (H-1PV) and minute virus of mice (MVM). However, LuIII displays enhanced oncolysis compared to H-1PV and MVM, a phenotype mapped to the major capsid viral protein 2 (VP2). This suggests that within LuIII VP2 are determinants for improved tumor lysis. To investigate this, the structure of the LuIII virus-like-particle was determined using single particle cryo-electron microscopy and image reconstruction to 3.17 Å resolution, and compared to the H-1PV and MVM structures. The LuIII VP2 structure, ordered from residue 37 to 587 (C-terminal), had the conserved VP topology and capsid morphology previously reported for other protoparvoviruses. This includes a core β-barrel and α-helix A, a depression at the icosahedral 2-fold and surrounding the 5-fold axes, and a single protrusion at the 3-fold axes. Comparative analysis identified surface loop differences among LuIII, H-1PV, and MVM at or close to the capsid 2- and 5-fold symmetry axes, and the shoulder of the 3-fold protrusions. The 2-fold differences cluster near the previously identified MVM sialic acid receptor binding pocket, and revealed potential determinants of protoparvovirus tumor tropism. Full article

(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)

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14 pages, 1991 KiB

Open AccessArticle

Gene Editing in Human Lymphoid Cells: Role for Donor DNA, Type of Genomic Nuclease and Cell Selection Method

by Anastasia Zotova¹, Elena Lopatukhina¹, Alexander Filatov², Musa Khaitov² and Dmitriy Mazurov^2,3,*

¹ Faculty of Biology, Lomonosov Moscow State University, 1–12 Leninskie Gory, 119991 Moscow, Russia

² NRC Institute of Immunology FMBA of Russia, 24 Kashirskoe shosse, 115472 Moscow, Russia

³ Cell and Gene Technology Group, Institute of Gene Biology RAS, 34/5 Vavilova Street, 119334 Moscow, Russia

Viruses 2017, 9(11), 325; https://doi.org/10.3390/v9110325 - 2 Nov 2017

Cited by 7 | Viewed by 6612

Abstract

Programmable endonucleases introduce DNA breaks at specific sites, which are repaired by non-homologous end joining (NHEJ) or homology recombination (HDR). Genome editing in human lymphoid cells is challenging as these difficult-to-transfect cells may also inefficiently repair DNA by HDR. Here, we estimated efficiencies [...] Read more.

Programmable endonucleases introduce DNA breaks at specific sites, which are repaired by non-homologous end joining (NHEJ) or homology recombination (HDR). Genome editing in human lymphoid cells is challenging as these difficult-to-transfect cells may also inefficiently repair DNA by HDR. Here, we estimated efficiencies and dynamics of knockout (KO) and knockin (KI) generation in human T and B cell lines depending on repair template, target loci and types of genomic endonucleases. Using zinc finger nuclease (ZFN), we have engineered Jurkat and CEM cells with the 8.2 kb human immunodeficiency virus type 1 (HIV-1) ∆Env genome integrated at the adeno-associated virus integration site 1 (AAVS1) locus that stably produce virus particles and mediate infection upon transfection with helper vectors. Knockouts generated by ZFN or clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) double nicking techniques were comparably efficient in lymphoid cells. However, unlike polyclonal sorted cells, gene-edited cells selected by cloning exerted tremendous deviations in functionality as estimated by replication of HIV-1 and human T cell leukemia virus type 1 (HTLV-1) in these cells. Notably, the recently reported high-fidelity eCas9 1.1 when combined to the nickase mutation displayed gene-dependent decrease in on-target activity. Thus, the balance between off-target effects and on-target efficiency of nucleases, as well as choice of the optimal method of edited cell selection should be taken into account for proper gene function validation in lymphoid cells. Full article

(This article belongs to the Section Animal Viruses)

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13 pages, 3766 KiB

Open AccessArticle

Helicase Domain of West Nile Virus NS3 Protein Plays a Role in Inhibition of Type I Interferon Signalling

by Yin Xiang Setoh

, Parthiban Periasamy, Nias Yong Gao Peng

, Alberto A. Amarilla, Andrii Slonchak

and Alexander A. Khromykh^*

Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia

Viruses 2017, 9(11), 326; https://doi.org/10.3390/v9110326 - 2 Nov 2017

Cited by 14 | Viewed by 6057

Abstract

West Nile virus (WNV) is a neurotropic flavivirus that can cause encephalitis in mammalian and avian hosts. In America, the virulent WNV strain (NY99) is causing yearly outbreaks of encephalitis in humans and horses, while in Australia the less virulent Kunjin strain of [...] Read more.

West Nile virus (WNV) is a neurotropic flavivirus that can cause encephalitis in mammalian and avian hosts. In America, the virulent WNV strain (NY99) is causing yearly outbreaks of encephalitis in humans and horses, while in Australia the less virulent Kunjin strain of WNV strain has not been associated with significant disease outbreaks until a recent 2011 large outbreak in horses (but not in humans) caused by NSW2011 strain. Using chimeric viruses between NY99 and NSW2011 strains we previously identified a role for the non-structural proteins of NY99 strain and especially the NS3 protein, in enhanced virus replication in type I interferon response-competent cells and increased virulence in mice. To further define the role of NY99 NS3 protein in inhibition of type I interferon response, we have generated and characterised additional chimeric viruses containing the protease or the helicase domains of NY99 NS3 on the background of the NSW2011 strain. The results identified the role for the helicase but not the protease domain of NS3 protein in the inhibition of type I interferon signalling and showed that helicase domain of the more virulent NY99 strain performs this function more efficiently than helicase domain of the less virulent NSW2011 strain. Further analysis with individual amino acid mutants identified two amino acid residues in the helicase domain primarily responsible for this difference. Using chimeric replicons, we also showed that the inhibition of type I interferon (IFN) signalling was independent of other known functions of NS3 in RNA replication and assembly of virus particles. Full article

(This article belongs to the Section Animal Viruses)

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22 pages, 4807 KiB

Open AccessArticle

Metagenomic Analysis of Therapeutic PYO Phage Cocktails from 1997 to 2014

by Julia Villarroel¹, Mette Voldby Larsen², Mogens Kilstrup³ and Morten Nielsen^1,4,*

¹ Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, Building 208, 2800 Kongens Lyngby, Denmark

² GoSeqIt ApS, Ved Klædebo 9, 2970 Hørsholm, Denmark

³ Department of Biotechnology and Biomedicine, Technical University of Denmark, Matematiktorvet, Building 301, 2800 Kongens Lyngby, Denmark

⁴ Instituto de Investigaciones Biotecnológicas, Universidad de San Martín, 1650 San Martín, Buenos Aires, Argentina

Viruses 2017, 9(11), 328; https://doi.org/10.3390/v9110328 - 3 Nov 2017

Cited by 59 | Viewed by 11828

Abstract

Phage therapy has regained interest in recent years due to the alarming spread of antibiotic resistance. Whilst phage cocktails are commonly sold in pharmacies in countries such as Georgia and Russia, this is not the case in western countries due to western regulatory [...] Read more.

Phage therapy has regained interest in recent years due to the alarming spread of antibiotic resistance. Whilst phage cocktails are commonly sold in pharmacies in countries such as Georgia and Russia, this is not the case in western countries due to western regulatory agencies requiring a thorough characterization of the drug. Here, DNA sequencing of constituent biological entities constitutes a first step. The pyophage (PYO) cocktail is one of the main commercial products of the Georgian Eliava Institute of Bacteriophage, Microbiology and Virology and is used to cure skin infections. Since its first production in the 1930s, the composition of the cocktail has been periodically modified to add phages effective against emerging pathogenic strains. In this paper, we compared the composition of three PYO cocktails from 1997 (PYO97), 2000 (PYO2000) and 2014 (PYO2014). Based on next generation sequencing, de novo assembly and binning of contigs into draft genomes based on tetranucleotide distance, thirty and twenty-nine phage draft genomes were predicted in PYO97 and PYO2014, respectively. Of these, thirteen and fifteen shared high similarity to known phages. Eleven draft genomes were found to be common in the two cocktails. One of these showed no similarity to publicly available phage genomes. Representatives of phages targeting E. faecalis, E. faecium, E. coli, Proteus, P. aeruginosa and S. aureus were found in both cocktails. Finally, we estimated larger overlap of the PYO2000 cocktail to PYO97 compared to PYO2014. Using next generation sequencing and metagenomics analysis, we were able to characterize and compare the content of PYO cocktails separated by 17 years in time. Even though the cocktail composition is upgraded every six months, we found it to remain relatively stable over the years. Full article

(This article belongs to the Special Issue Bacteriophage Genomes and Genomics: News from the Wild)

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10 pages, 733 KiB

Open AccessArticle

Characterization of Nucleoside Reverse Transcriptase Inhibitor-Associated Mutations in the RNase H Region of HIV-1 Subtype C Infected Individuals

by Sinaye Ngcapu^1,2,*,†, Kristof Theys^3,†

, Pieter Libin^3,4

, Vincent C. Marconi⁵, Henry Sunpath⁶, Thumbi Ndung’u^1,7,8,9

and Michelle L. Gordon¹

¹ HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, Durban 4013, South Africa

² Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Private Bag X7, Congella, Durban 4013, South Africa

³ Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven–University of Leuven, 3000 Leuven, Belgium

⁴ Artificial Intelligence Lab, Department of Computer Science, Vrije Universiteit Brussel, Brussels, 1050 Elsene, Belgium

⁵ Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA 30322, USA

⁶ Infectious Diseases Unit, Nelson Mandela School of Medicine, University of KwaZulu-Natal, Private Bag X7, Congella, Durban 4013, South Africa

⁷ Africa Health Research Institute, University of KwaZulu-Natal, Private Bag X7, Congella, Durban 4013, South Africa

⁸ Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA 01239, USA

⁹ Max Planck Institute for Infection Biology, Chariteplatz, D-10117 Berlin, Germany

^† These authors contributed equally to this work.

Viruses 2017, 9(11), 330; https://doi.org/10.3390/v9110330 - 8 Nov 2017

Cited by 6 | Viewed by 4560

Abstract

The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. [...] Read more.

The South African national treatment programme includes nucleoside reverse transcriptase inhibitors (NRTIs) in both first and second line highly active antiretroviral therapy regimens. Mutations in the RNase H domain have been associated with resistance to NRTIs but primarily in HIV-1 subtype B studies. Here, we investigated the prevalence and association of RNase H mutations with NRTI resistance in sequences from HIV-1 subtype C infected individuals. RNase H sequences from 112 NRTI treated but virologically failing individuals and 28 antiretroviral therapy (ART)-naive individuals were generated and analysed. In addition, sequences from 359 subtype C ART-naive sequences were downloaded from Los Alamos database to give a total of 387 sequences from ART-naive individuals for the analysis. Fisher’s exact test was used to identify mutations and Bayesian network learning was applied to identify novel NRTI resistance mutation pathways in RNase H domain. The mutations A435L, S468A, T470S, L484I, A508S, Q509L, L517I, Q524E and E529D were more prevalent in sequences from treatment-experienced compared to antiretroviral treatment naive individuals, however, only the E529D mutation remained significant after correction for multiple comparison. Our findings suggest a potential interaction between E529D and NRTI-treatment; however, site-directed mutagenesis is needed to understand the impact of this RNase H mutation. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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15 pages, 2628 KiB

Open AccessArticle

Rapid Construction of Complex Plant RNA Virus Infectious cDNA Clones for Agroinfection Using a Yeast-E. coli-Agrobacterium Shuttle Vector

by Kai Sun¹, Danyang Zhao¹, Yong Liu², Changjun Huang²

, Wei Zhang³ and Zhenghe Li^1,*

¹ State Key Laboratory of Rice Biology, Institute of Biotechnology, Zhejiang University, Hangzhou 310058, China

² Yunnan Academy of Tobacco Agricultural Sciences, Key Laboratory of Tobacco Biotechnological Breeding, National Tobacco Genetic Engineering Research Center, Kunming 650021, China

³ Sichuan Plant Protection Station, Chengdu 610041, China

Viruses 2017, 9(11), 332; https://doi.org/10.3390/v9110332 - 7 Nov 2017

Cited by 44 | Viewed by 13180

Abstract

The availability of infectious full-length clone is indispensable for reverse genetics studies of virus biology, pathology and construction of viral vectors. However, for RNA viruses with large genome sizes or those exhibiting inherent cloning difficulties, procedure to generate biologically active complementary DNA (cDNA) [...] Read more.

The availability of infectious full-length clone is indispensable for reverse genetics studies of virus biology, pathology and construction of viral vectors. However, for RNA viruses with large genome sizes or those exhibiting inherent cloning difficulties, procedure to generate biologically active complementary DNA (cDNA) clones can be time-consuming or technically challenging. Here we have constructed a yeast-Escherichia coli-Agrobacterium shuttle vector that enables highly efficient homologous recombination in yeast for assembly of Agrobacterium compatible plant virus clones. Using this vector, we show that infectious cDNA clones of a plant negative-stranded RNA virus, sonchus yellow net rhabdovirus, can be rapidly assembled. In addition, one-step assembly of infectious clones of potato virus Y in yeast, either with or without intron, was readily achieved from as many as eight overlapping DNA fragments. More importantly, the recovered yeast plasmids can be transformed directly into Agrobacterium for inoculation, thereby obviating the E. coli cloning steps and associated toxicity issues. This method is rapid, highly efficient and cost-effective and should be readily applicable to a broad range of plant viruses. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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20 pages, 15585 KiB

Open AccessArticle

Begomoviral Movement Protein Effects in Human and Plant Cells: Towards New Potential Interaction Partners

by Susanna Krapp¹, Christian Schuy¹, Eva Greiner¹, Irina Stephan², Barbara Alberter², Christina Funk³, Manfred Marschall⁴, Christina Wege²

, Susanne M. Bailer³, Tatjana Kleinow²

and Björn Krenz^5,*

¹ Department Biologie, Lehrstuhl Biochemie, Universität Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany

² Abteilung Molekularbiologie und Virologie der Pflanzen, Institut für Biomaterialien und Biomolekulare Systeme, Universität Stuttgart, Pfaffenwaldring 57, 70569 Stuttgart, Germany

³ Institute for Interfacial Engineering and Plasma Technology IGVP, Universität Stuttgart, Nobelstrasse 12, 70569 Stuttgart, Germany

⁴ Institute for Clinical and Molecular Virology, Universität Erlangen-Nürnberg, 91054 Erlangen, Germany

⁵ Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Inhoffenstr. 7 B, 38124 Braunschweig, Germany

Viruses 2017, 9(11), 334; https://doi.org/10.3390/v9110334 - 9 Nov 2017

Cited by 14 | Viewed by 8662

Abstract

Geminiviral single-stranded circular DNA genomes replicate in nuclei so that the progeny DNA has to cross both the nuclear envelope and the plasmodesmata for systemic spread within plant tissues. For intra- and intercellular transport, two proteins are required: a nuclear shuttle protein (NSP) [...] Read more.

Geminiviral single-stranded circular DNA genomes replicate in nuclei so that the progeny DNA has to cross both the nuclear envelope and the plasmodesmata for systemic spread within plant tissues. For intra- and intercellular transport, two proteins are required: a nuclear shuttle protein (NSP) and a movement protein (MP). New characteristics of ectopically produced Abutilon mosaic virus (AbMV) MP (MP^AbMV), either authentically expressed or fused to a yellow fluorescent protein or epitope tags, respectively, were determined by localization studies in mammalian cell lines in comparison to plant cells. Wild-type MP^AbMV and the distinct MP^AbMV: reporter protein fusions appeared as curled threads throughout mammalian cells. Co-staining with cytoskeleton markers for actin, intermediate filaments, or microtubules identified these threads as re-organized microtubules. These were, however, not stabilized by the viral MP, as demonstrated by nocodazole treatment. The MP of a related bipartite New World begomovirus, Cleome leaf crumple virus (ClLCrV), resulted in the same intensified microtubule bundling, whereas that of a nanovirus did not. The C-terminal section of MP^AbMV, i.e., the protein’s oligomerization domain, was dispensable for the effect. However, MP expression in plant cells did not affect the microtubules network. Since plant epidermal cells are quiescent whilst mammalian cells are proliferating, the replication-associated protein Rep^AbMV protein was then co-expressed with MP^AbMV to induce cell progression into S-phase, thereby inducing distinct microtubule bundling without MP recruitment to the newly formed threads. Co-immunoprecipitation of MP^AbMV in the presence of Rep^AbMV, followed by mass spectrometry identified potential novel MP^AbMV-host interaction partners: the peptidyl-prolyl cis-trans isomerase NIMA-interacting 4 (Pin4) and stomatal cytokinesis defective 2 (SCD2) proteins. Possible roles of these putative interaction partners in the begomoviral life cycle and cytoskeletal association modes are discussed. Full article

(This article belongs to the Special Issue Geminiviruses)

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13 pages, 2753 KiB

Open AccessArticle

Crystal Structure of the Full-Length Feline Immunodeficiency Virus Capsid Protein Shows an N-Terminal β-Hairpin in the Absence of N-Terminal Proline

by Christelle Folio¹, Natalia Sierra², Marie Dujardin¹, Guzman Alvarez²

and Christophe Guillon^1,*

¹ Equipe Rétrovirus et Biochimie Structurale, Université de Lyon, CNRS, MMSB, UMR 5086 CNRS/Université de Lyon, IBCP, Lyon 69367 CEDEX 07, France

² Laboratorio de Moléculas Bioactivas, Centro Universitario Regional Litoral Norte, Universidad de la República, Paysandú 60000, Uruguay

Viruses 2017, 9(11), 335; https://doi.org/10.3390/v9110335 - 9 Nov 2017

Cited by 10 | Viewed by 6417

Abstract

Feline immunodeficiency virus (FIV) is a member of the Retroviridae family. It is the causative agent of an acquired immunodeficiency syndrome (AIDS) in cats and wild felines. Its capsid protein (CA) drives the assembly of the viral particle, which is a critical step [...] Read more.

Feline immunodeficiency virus (FIV) is a member of the Retroviridae family. It is the causative agent of an acquired immunodeficiency syndrome (AIDS) in cats and wild felines. Its capsid protein (CA) drives the assembly of the viral particle, which is a critical step in the viral replication cycle. Here, the first atomic structure of full-length FIV CA to 1.67 Å resolution is determined. The crystallized protein exhibits an original tetrameric assembly, composed of dimers which are stabilized by an intermolecular disulfide bridge induced by the crystallogenesis conditions. The FIV CA displays a standard α-helical CA topology with two domains, separated by a linker shorter than other retroviral CAs. The β-hairpin motif at its amino terminal end, which interacts with nucleotides in HIV-1, is unusually long in FIV CA. Interestingly, this functional β-motif is formed in this construct in the absence of the conserved N-terminal proline. The FIV CA exhibits a cis Arg–Pro bond in the CypA-binding loop, which is absent in known structures of lentiviral CAs. This structure represents the first tri-dimensional structure of a functional, full-length FIV CA. Full article

(This article belongs to the Section Animal Viruses)

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21 pages, 2775 KiB

Open AccessArticle

Antibody Competition Reveals Surface Location of HPV L2 Minor Capsid Protein Residues 17–36

by Stephanie M. Bywaters^1,*, Sarah A. Brendle², Kerstin P. Tossi³, Jennifer Biryukov¹, Craig Meyers¹ and Neil D. Christensen²

¹ Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA

² Jake Gittlen Laboratories for Cancer Research, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA

³ Medigene AG, Martinsried, 82152 Planegg, Germany

Viruses 2017, 9(11), 336; https://doi.org/10.3390/v9110336 - 10 Nov 2017

Cited by 10 | Viewed by 6149

Abstract

The currently available nonavalent human papillomavirus (HPV) vaccine exploits the highly antigenic L1 major capsid protein to promote high-titer neutralizing antibodies, but is limited to the HPV types included in the vaccine since the responses are highly type-specific. The limited cross-protection offered by [...] Read more.

The currently available nonavalent human papillomavirus (HPV) vaccine exploits the highly antigenic L1 major capsid protein to promote high-titer neutralizing antibodies, but is limited to the HPV types included in the vaccine since the responses are highly type-specific. The limited cross-protection offered by the L1 virus-like particle (VLP) vaccine warrants further investigation into cross-protective L2 epitopes. The L2 proteins are yet to be fully characterized as to their precise placement in the virion. Adding to the difficulties in localizing L2, studies have suggested that L2 epitopes are not well exposed on the surface of the mature capsid prior to cellular engagement. Using a series of competition assays between previously mapped anti-L1 monoclonal antibodies (mAbs) (H16.V5, H16.U4 and H16.7E) and novel anti-L2 mAbs, we probed the capsid surface for the location of an L2 epitope (aa17–36). The previously characterized L1 epitopes together with our competition data is consistent with a proposed L2 epitope within the canyons of pentavalent capsomers. Full article

(This article belongs to the Section Animal Viruses)

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21 pages, 1332 KiB

Open AccessArticle

Combined Proteomics/Genomics Approach Reveals Proteomic Changes of Mature Virions as a Novel Poxvirus Adaptation Mechanism

by Marica Grossegesse¹, Joerg Doellinger^1,2, Alona Tyshaieva¹, Lars Schaade³ and Andreas Nitsche^1,*

¹ Centre for Biological Threats and Special Pathogens, Highly Pathogenic Viruses (ZBS 1), Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany

² Centre for Biological Threats and Special Pathogens, Proteomics and Spectroscopy (ZBS 6), Robert Koch Institute, Seestr. 10, 13353 Berlin, Germany

³ Centre for Biological Threats and Special Pathogens (ZBS), Robert Koch Institute, Nordufer 20, 13353 Berlin, Germany

Viruses 2017, 9(11), 337; https://doi.org/10.3390/v9110337 - 10 Nov 2017

Cited by 6 | Viewed by 5564

Abstract

DNA viruses, like poxviruses, possess a highly stable genome, suggesting that adaptation of virus particles to specific cell types is not restricted to genomic changes. Cowpox viruses are zoonotic poxviruses with an extraordinarily broad host range, demonstrating their adaptive potential in vivo. To [...] Read more.

DNA viruses, like poxviruses, possess a highly stable genome, suggesting that adaptation of virus particles to specific cell types is not restricted to genomic changes. Cowpox viruses are zoonotic poxviruses with an extraordinarily broad host range, demonstrating their adaptive potential in vivo. To elucidate adaptation mechanisms of poxviruses, we isolated cowpox virus particles from a rat and passaged them five times in a human and a rat cell line. Subsequently, we analyzed the proteome and genome of the non-passaged virions and each passage. While the overall viral genome sequence was stable during passaging, proteomics revealed multiple changes in the virion composition. Interestingly, an increased viral fitness in human cells was observed in the presence of increased immunomodulatory protein amounts. As the only minor variant with increasing frequency during passaging was located in a viral RNA polymerase subunit and, moreover, most minor variants were found in transcription-associated genes, protein amounts were presumably regulated at transcription level. This study is the first comparative proteome analysis of virus particles before and after cell culture propagation, revealing proteomic changes as a novel poxvirus adaptation mechanism. Full article

(This article belongs to the Special Issue Smallpox and Emerging Zoonotic Orthopoxviruses: What Is Coming Next?)

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19 pages, 3245 KiB

Open AccessArticle

The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection

by Ben J. Trigg^1,†, Katharina B. Lauer^1,†, Paula Fernandes dos Santos², Heather Coleman¹, Gabriel Balmus^3,4

, Daniel S. Mansur²

and Brian J. Ferguson^1,*

¹ Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK

² Laboratory of Immunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Santa Catarina 88040-900, Brazil

³ Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK

⁴ Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK

^† These authors contributed equally to this work.

Viruses 2017, 9(11), 342; https://doi.org/10.3390/v9110342 - 16 Nov 2017

Cited by 8 | Viewed by 7667

Abstract

Herpes simplex virus 1 (HSV-1) has extensive interactions with the host DNA damage response (DDR) machinery that can be either detrimental or beneficial to the virus. Proteins in the homologous recombination pathway are known to be required for efficient replication of the viral [...] Read more.

Herpes simplex virus 1 (HSV-1) has extensive interactions with the host DNA damage response (DDR) machinery that can be either detrimental or beneficial to the virus. Proteins in the homologous recombination pathway are known to be required for efficient replication of the viral genome, while different members of the classical non-homologous end-joining (c-NHEJ) pathway have opposing effects on HSV-1 infection. Here, we have investigated the role of the recently-discovered c-NHEJ component, PAXX (Paralogue of XRCC4 and XLF), which we found to be excluded from the nucleus during HSV-1 infection. We have established that cells lacking PAXX have an intact innate immune response to HSV-1 but show a defect in viral genome replication efficiency. Counterintuitively, PAXX^−/− cells were able to produce greater numbers of infectious virions, indicating that PAXX acts to restrict HSV-1 infection in a manner that is different from other c-NHEJ factors. Full article

(This article belongs to the Special Issue Viruses and the DNA Damage Response)

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13 pages, 2840 KiB

Open AccessArticle

The Ms6 Mycolyl-Arabinogalactan Esterase LysB is Essential for an Efficient Mycobacteriophage-Induced Lysis

by Adriano M. Gigante¹, Cheri M. Hampton²

, Rebecca S. Dillard², Filipa Gil¹, Maria João Catalão¹, José Moniz-Pereira¹, Elizabeth R. Wright² and Madalena Pimentel^1,*

¹ Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, 1649-003, Portugal

² Division of Pediatric Infectious Diseases, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta, GA, 30345, USA

Viruses 2017, 9(11), 343; https://doi.org/10.3390/v9110343 - 17 Nov 2017

Cited by 30 | Viewed by 5799

Abstract

All dsDNA phages encode two proteins involved in host lysis, an endolysin and a holin that target the peptidoglycan and cytoplasmic membrane, respectively. Bacteriophages that infect Gram-negative bacteria encode additional proteins, the spanins, involved in disruption of the outer membrane. Recently, a gene [...] Read more.

All dsDNA phages encode two proteins involved in host lysis, an endolysin and a holin that target the peptidoglycan and cytoplasmic membrane, respectively. Bacteriophages that infect Gram-negative bacteria encode additional proteins, the spanins, involved in disruption of the outer membrane. Recently, a gene located in the lytic cassette was identified in the genomes of mycobacteriophages, which encodes a protein (LysB) with mycolyl-arabinogalactan esterase activity. Taking in consideration the complex mycobacterial cell envelope that mycobacteriophages encounter during their life cycle, it is valuable to evaluate the role of these proteins in lysis. In the present work, we constructed an Ms6 mutant defective on lysB and showed that Ms6 LysB has an important role in lysis. In the absence of LysB, lysis still occurs but the newly synthesized phage particles are deficiently released to the environment. Using cryo-electron microscopy and tomography to register the changes in the lysis phenotype, we show that at 150 min post-adsorption, mycobacteria cells are incompletely lysed and phage particles are retained inside the cell, while cells infected with Ms6wt are completely lysed. Our results confirm that Ms6 LysB is necessary for an efficient lysis of Mycobacterium smegmatis, acting, similarly to spanins, in the third step of the lysis process. Full article

(This article belongs to the Section Bacterial Viruses)

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15 pages, 923 KiB

Open AccessArticle

Epidemiological Investigations of Four Cowpox Virus Outbreaks in Alpaca Herds, Germany

by Almut Prkno^1,†, Donata Hoffmann^2,†, Daniela Goerigk³, Matthias Kaiser¹, Anne Catherine Franscisca Van Maanen⁴, Kathrin Jeske⁵, Maria Jenckel², Florian Pfaff²

, Thomas W. Vahlenkamp⁶, Martin Beer², Rainer G. Ulrich⁵

, Alexander Starke¹ and Martin Pfeffer^4,*

¹ Clinic for Ruminants and Swine, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 11, 04103 Leipzig, Germany

² Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald-Insel Riems, Germany

³ Veterinary practice Dr. Daniela Goerigk, Naundorfer Str. 9, 04668 Schkortitz, Germany

⁴ Institute of Animal Hygiene and Veterinary Public Health, Centre for Veterinary Public Health, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 1, 04103 Leipzig, Germany

⁵ Institute of Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493 Greifswald-Insel Riems, Germany

⁶ Institute of Virology, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 29, 04103 Leipzig, Germany

^† These authors contributed equally to this work.

Viruses 2017, 9(11), 344; https://doi.org/10.3390/v9110344 - 18 Nov 2017

Cited by 25 | Viewed by 7413

Abstract

Four cowpox virus (CPXV) outbreaks occurred in unrelated alpaca herds in Eastern Germany during 2012–2017. All incidents were initially noticed due to severe, generalized, and finally lethal CPXV infections, which were confirmed by testing of tissue and serum samples. As CPXV-infection has been [...] Read more.

Four cowpox virus (CPXV) outbreaks occurred in unrelated alpaca herds in Eastern Germany during 2012–2017. All incidents were initially noticed due to severe, generalized, and finally lethal CPXV infections, which were confirmed by testing of tissue and serum samples. As CPXV-infection has been described in South American camelids (SACs) only three times, all four herds were investigated to gain a deeper understanding of CPXV epidemiology in alpacas. The different herds were investigated twice, and various samples (serum, swab samples, and crusts of suspicious pox lesions, feces) were taken to identify additionally infected animals. Serum was used to detect CPXV-specific antibodies by performing an indirect immunofluorescence assay (iIFA); swab samples, crusts, and feces were used for detection of CPXV-specific DNA in a real-time PCR. In total, 28 out of 107 animals could be identified as affected by CPXV, by iIFA and/or PCR. Herd seroprevalence ranged from 16.1% to 81.2%. To investigate the potential source of infection, wild small mammals were trapped around all alpaca herds. In two herds, CPXV-specific antibodies were found in the local rodent population. In the third herd, CPXV could be isolated from a common vole (Microtus arvalis) found drowned in a water bucket used to water the alpacas. Full genome sequencing and comparison with the genome of a CPXV from an alpaca from the same herd reveal 99.997% identity, providing further evidence that the common vole is a reservoir host and infection source of CPXV. Only in the remaining fourth herd, none of the trapped rodents were found to be CPXV-infected. Rodents, as ubiquitous reservoir hosts, in combination with increasingly popular alpacas, as susceptible species, suggest an enhanced risk of future zoonotic infections. Full article

(This article belongs to the Special Issue Smallpox and Emerging Zoonotic Orthopoxviruses: What Is Coming Next?)

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19 pages, 2191 KiB

Open AccessArticle

Characterization of Ovine A3Z1 Restriction Properties against Small Ruminant Lentiviruses (SRLVs)

by Lorena De Pablo-Maiso¹, Idoia Glaria¹, Helena Crespo¹, Estanislao Nistal-Villán²

, Valgerdur Andrésdóttir³, Damián De Andrés¹

, Beatriz Amorena¹ and Ramsés Reina^1,*

¹ Instituto de Agrobiotecnología, UPNA-CSIC-Gobierno de Navarra, 31192 Mutilva, Spain

² Sección de Microbiología, Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo C.E.U. Ctra, Boadilla del Monte Km, 28003 Madrid, Spain

³ Institute for Experimental Pathology, University of Iceland, Keldur, 112 Reykjavik, Iceland

Viruses 2017, 9(11), 345; https://doi.org/10.3390/v9110345 - 17 Nov 2017

Cited by 6 | Viewed by 4621

Abstract

Intrinsic factors of the innate immune system include the apolipoprotein B editing enzyme catalytic polypeptide-like 3 (APOBEC3) protein family. APOBEC3 inhibits replication of different virus families by cytosine deamination of viral DNA and a not fully characterized cytosine deamination-independent mechanism. Sheep are susceptible [...] Read more.

Intrinsic factors of the innate immune system include the apolipoprotein B editing enzyme catalytic polypeptide-like 3 (APOBEC3) protein family. APOBEC3 inhibits replication of different virus families by cytosine deamination of viral DNA and a not fully characterized cytosine deamination-independent mechanism. Sheep are susceptible to small ruminant lentivirus (SRLVs) infection and contain three APOBEC3 genes encoding four proteins (A3Z1, Z2, Z3 and Z2-Z3) with yet not deeply described antiviral properties. Using sheep blood monocytes and in vitro-derived macrophages, we found that A3Z1 expression is associated with lower viral replication in this cellular type. A3Z1 transcripts may also contain spliced variants (A3Z1Tr) lacking the cytidine deaminase motif. A3Z1 exogenous expression in fully permissive fibroblast-like cells restricted SRLVs infection while A3Z1Tr allowed infection. A3Z1Tr was induced after SRLVs infection or stimulation of blood-derived macrophages with interferon gamma (IFN-γ). Interaction between truncated isoform and native A3Z1 protein was detected as well as incorporation of both proteins into virions. A3Z1 and A3Z1Tr interacted with SRLVs Vif, but this interaction was not associated with degradative properties. Similar A3Z1 truncated isoforms were also present in human and monkey cells suggesting a conserved alternative splicing regulation in primates. A3Z1-mediated retroviral restriction could be constrained by different means, including gene expression and specific alternative splicing regulation, leading to truncated protein isoforms lacking a cytidine-deaminase motif. Full article

(This article belongs to the Section Animal Viruses)

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10 pages, 1369 KiB

Open AccessArticle

RNA Virus Evolution via a Quasispecies-Based Model Reveals a Drug Target with a High Barrier to Resistance

by Richard J. Bingham^1,2,3

, Eric C. Dykeman^1,3 and Reidun Twarock^1,2,3,*

¹ Departments of Mathematics, University of York, York YO10 5DD, UK

² Department of Biology, University of York, York YO10 5DD, UK

³ York Cross-disciplinary Centre for Systems Analysis, University of York, York YO10 5GE, UK

Viruses 2017, 9(11), 347; https://doi.org/10.3390/v9110347 - 17 Nov 2017

Cited by 19 | Viewed by 7269

Abstract

The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an [...] Read more.

The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly. We introduce here a quasispecies-based model of a viral infection that incorporates structural and mechanistic knowledge of packaging signal function in assembly to construct a phenotype-fitness map, capturing the impact of this RNA code on assembly yield and efficiency. Details of viral replication and assembly inside an infected host cell are coupled with a population model of a viral infection, allowing the occurrence of therapy resistance to be assessed in response to drugs inhibiting packaging signal recognition. Stochastic simulations of viral quasispecies evolution in chronic HCV infection under drug action and/or immune clearance reveal that drugs targeting all RNA signals in the assembly code collectively have a high barrier to drug resistance, even though each packaging signal in isolation has a lower barrier than conventional drugs. This suggests that drugs targeting the RNA signals in the assembly code could be promising routes for exploitation in anti-viral drug design. Full article

(This article belongs to the Special Issue Mathematical Modeling of Viral Infections)

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14 pages, 1030 KiB

Open AccessArticle

Diversity of dsDNA Viruses in a South African Hot Spring Assessed by Metagenomics and Microscopy

by Olivier Zablocki

, Leonardo Joaquim Van Zyl

, Bronwyn Kirby and Marla Trindade^*

Institute for Microbial Biotechnology and Metagenomics, Department of Biotechnology, University of the Western Cape, 7535 Bellville, South Africa

Viruses 2017, 9(11), 348; https://doi.org/10.3390/v9110348 - 18 Nov 2017

Cited by 21 | Viewed by 7850 | Correction

Abstract

The current view of virus diversity in terrestrial hot springs is limited to a few sampling sites. To expand our current understanding of hot spring viral community diversity, this study aimed to investigate the first African hot spring (Brandvlei hot spring; 60 °C, [...] Read more.

The current view of virus diversity in terrestrial hot springs is limited to a few sampling sites. To expand our current understanding of hot spring viral community diversity, this study aimed to investigate the first African hot spring (Brandvlei hot spring; 60 °C, pH 5.7) by means of electron microscopy and sequencing of the virus fraction. Microscopy analysis revealed a mixture of regular- and ‘jumbo’-sized tailed morphotypes (Caudovirales), lemon-shaped virions (Fuselloviridae-like; salterprovirus-like) and pleiomorphic virus-like particles. Metavirome analysis corroborated the presence of His1-like viruses and has expanded the current clade of salterproviruses using a polymerase B gene phylogeny. The most represented viral contig was to a cyanophage genome fragment, which may underline basic ecosystem functioning provided by these viruses. Furthermore, a putative Gemmata-related phage was assembled with high coverage, a previously undocumented phage-host association. This study demonstrated that a moderately thermophilic spring environment contained a highly novel pool of viruses and should encourage future characterization of a wider temperature range of hot springs throughout the world. Full article

(This article belongs to the Section Bacterial Viruses)

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17 pages, 873 KiB

Open AccessArticle

The Role of Infected Cell Proliferation in the Clearance of Acute HBV Infection in Humans

by Ashish Goyal^1,*

, Ruy M. Ribeiro^1,2 and Alan S. Perelson¹

¹ Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA

² Laboratório de Biomatemática, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal

Viruses 2017, 9(11), 350; https://doi.org/10.3390/v9110350 - 18 Nov 2017

Cited by 34 | Viewed by 7746

Abstract

Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it [...] Read more.

Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection data together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. In conclusion, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell. Full article

(This article belongs to the Special Issue Mathematical Modeling of Viral Infections)

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18 pages, 9150 KiB

Open AccessArticle

Neurotropism In Vitro and Mouse Models of Severe and Mild Infection with Clinical Strains of Enterovirus 71

by Pin Yu, Linlin Bao, Lili Xu, Fengdi Li, Qi Lv, Wei Deng, Yanfeng Xu and Chuan Qin^*

Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Beijing 100021, China

Viruses 2017, 9(11), 351; https://doi.org/10.3390/v9110351 - 20 Nov 2017

Cited by 15 | Viewed by 5617

Abstract

Enterovirus 71 (EV71) is a common etiological agent of hand, foot, and mouth disease and fatal neurological diseases in children. The neuropathogenicity of severe EV71 infection has been documented, but studies comparing mouse models of severe and mild EV71 infection are lacking. The [...] Read more.

Enterovirus 71 (EV71) is a common etiological agent of hand, foot, and mouth disease and fatal neurological diseases in children. The neuropathogenicity of severe EV71 infection has been documented, but studies comparing mouse models of severe and mild EV71 infection are lacking. The aim of the study was to investigate the neurovirulence of EV71 strains and the differences in serum cytokine and chemokine levels in mouse models of severe and mild EV71 infection. Nine EV71 isolates belonging to the C4 subgenogroup (proposed as genotype D) displayed infectivity in human neuroblastoma SK-N-SH cells; moreover, ultrastructural observation confirmed viral particle replication. The survival rate of the severe model was 71.43% (5/7), and 60% (3/5) of the surviving severe model mice displayed sequelae of paralysis, whereas the only symptom in mild model mice was ruffled fur. Dynamic detection of serum cytokine and chemokine levels demonstrated that interleukin (IL)-5, IL-13, IL-6, monocyte chemotactic protein 1 (MCP-1), and chemokine (C-C motif) ligand 5 (also called Regulated upon Activation, Normal T-cell Expressed, and Secreted (CCL5/RANTES) were significantly up-regulated at the early period of infection, indicating that these factors might herald a severe outcome. Our findings suggest that elevated cytokines and chemokines may have potential value as prognostic markers in mouse models. Full article

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18 pages, 2787 KiB

Open AccessArticle

Pressure for Pattern-Specific Intertypic Recombination between Sabin Polioviruses: Evolutionary Implications

by Ekaterina Korotkova^1,2,†, Majid Laassri^3,†

, Tatiana Zagorodnyaya³, Svetlana Petrovskaya³, Elvira Rodionova³, Elena Cherkasova⁴, Anatoly Gmyl^2,5, Olga E. Ivanova^2,5, Tatyana P. Eremeeva², Galina Y. Lipskaya¹, Vadim I. Agol^1,2,*

and Konstantin Chumakov^3,*

¹ AN Belozersky Institute of Physical-Chemical Biology, MV Lomonosov Moscow State University, Moscow 119899, Russia

² Institute of Poliomyelitis and Viral Encephalitides of MP Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow 108819, Russia

³ US Food and Drug Administration, Silver Spring, MD 20993, USA

⁴ National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20895, USA

⁵ IM Sechenov First Moscow State Medical University, Moscow 119991, Russia

^† These authors contributed equally to this report.

Viruses 2017, 9(11), 353; https://doi.org/10.3390/v9110353 - 22 Nov 2017

Cited by 20 | Viewed by 5073

Abstract

Complete genomic sequences of a non-redundant set of 70 recombinants between three serotypes of attenuated Sabin polioviruses as well as location (based on partial sequencing) of crossover sites of 28 additional recombinants were determined and compared with the previously published data. It is [...] Read more.

Complete genomic sequences of a non-redundant set of 70 recombinants between three serotypes of attenuated Sabin polioviruses as well as location (based on partial sequencing) of crossover sites of 28 additional recombinants were determined and compared with the previously published data. It is demonstrated that the genomes of Sabin viruses contain distinct strain-specific segments that are eliminated by recombination. The presumed low fitness of these segments could be linked to mutations acquired upon derivation of the vaccine strains and/or may have been present in wild-type parents of Sabin viruses. These “weak” segments contribute to the propensity of these viruses to recombine with each other and with other enteroviruses as well as determine the choice of crossover sites. The knowledge of location of such segments opens additional possibilities for the design of more genetically stable and/or more attenuated variants, i.e., candidates for new oral polio vaccines. The results also suggest that the genome of wild polioviruses, and, by generalization, of other RNA viruses, may harbor hidden low-fitness segments that can be readily eliminated only by recombination. Full article

(This article belongs to the Special Issue Viral Recombination: Ecology, Evolution and Pathogenesis)

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20 pages, 3112 KiB

Open AccessReview

Protoparvovirus Cell Entry

by Carlos Ros^1,*, Nooshin Bayat², Raphael Wolfisberg³ and José M. Almendral^2,*

¹ Department of Chemistry and Biochemistry, University of Bern, 3012 Bern, Switzerland

² Centro de Biología Molecular “Severo Ochoa”, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain

³ Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, 1165 Copenhagen, Denmark

Viruses 2017, 9(11), 313; https://doi.org/10.3390/v9110313 - 26 Oct 2017

Cited by 40 | Viewed by 11613

Abstract

The Protoparvovirus (PtPV) genus of the Parvoviridae family of viruses includes important animal pathogens and reference molecular models for the entire family. Some virus members of the PtPV genus have arisen as promising tools to treat tumoral processes, as they exhibit marked oncotropism [...] Read more.

The Protoparvovirus (PtPV) genus of the Parvoviridae family of viruses includes important animal pathogens and reference molecular models for the entire family. Some virus members of the PtPV genus have arisen as promising tools to treat tumoral processes, as they exhibit marked oncotropism and oncolytic activities while being nonpathogenic for humans. The PtPVs invade and replicate within the nucleus making extensive use of the transport, transcription and replication machineries of the host cells. In order to reach the nucleus, PtPVs need to cross over several intracellular barriers and traffic through different cell compartments, which limit their infection efficiency. In this review we summarize molecular interactions, capsid structural transitions and hijacking of cellular processes, by which the PtPVs enter and deliver their single-stranded DNA genome into the host cell nucleus. Understanding mechanisms that govern the complex PtPV entry will be instrumental in developing approaches to boost their anticancer therapeutic potential and improving their safety profile. Full article

(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)

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19 pages, 598 KiB

Open AccessReview

Virus Infection and Death Receptor-Mediated Apoptosis

by Xingchen Zhou^†, Wenbo Jiang^†, Zhongshun Liu, Shuai Liu and Xiaozhen Liang^*

¹ Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China

^† These authors contributed equally to this work.

Viruses 2017, 9(11), 316; https://doi.org/10.3390/v9110316 - 27 Oct 2017

Cited by 157 | Viewed by 11517

Abstract

Virus infection can trigger extrinsic apoptosis. Cell-surface death receptors of the tumor necrosis factor family mediate this process. They either assist persistent viral infection or elicit the elimination of infected cells by the host. Death receptor-mediated apoptosis plays an important role in viral [...] Read more.

Virus infection can trigger extrinsic apoptosis. Cell-surface death receptors of the tumor necrosis factor family mediate this process. They either assist persistent viral infection or elicit the elimination of infected cells by the host. Death receptor-mediated apoptosis plays an important role in viral pathogenesis and the host antiviral response. Many viruses have acquired the capability to subvert death receptor-mediated apoptosis and evade the host immune response, mainly by virally encoded gene products that suppress death receptor-mediated apoptosis. In this review, we summarize the current information on virus infection and death receptor-mediated apoptosis, particularly focusing on the viral proteins that modulate death receptor-mediated apoptosis. Full article

(This article belongs to the Special Issue Viral Infection and Apoptosis)

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29 pages, 2390 KiB

Open AccessReview

Hazard Characterization of Modified Vaccinia Virus Ankara Vector: What Are the Knowledge Gaps?

by Malachy I. Okeke^1,*, Arinze S. Okoli¹, Diana Diaz²

, Collins Offor³, Taiwo G. Oludotun³, Morten Tryland^1,4, Thomas Bøhn¹ and Ugo Moens²

¹ Genome Editing Research Group, GenØk-Center for Biosafety, Siva Innovation Center, N-9294 Tromso, Norway

² Molecular Inflammation Research Group, Institute of Medical Biology, University i Tromsø (UiT)—The Arctic University of Norway, N-9037 Tromso, Norway

³ Department of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences Piaristengasse 1, A-3500 Krems, Austria

⁴ Artic Infection Biology, Department of Artic and Marine Biology, UIT—The Artic University of Norway, N-9037 Tromso, Norway

Viruses 2017, 9(11), 318; https://doi.org/10.3390/v9110318 - 29 Oct 2017

Cited by 13 | Viewed by 9626

Abstract

Modified vaccinia virus Ankara (MVA) is the vector of choice for human and veterinary applications due to its strong safety profile and immunogenicity in vivo. The use of MVA and MVA-vectored vaccines against human and animal diseases must comply with regulatory requirements as [...] Read more.

Modified vaccinia virus Ankara (MVA) is the vector of choice for human and veterinary applications due to its strong safety profile and immunogenicity in vivo. The use of MVA and MVA-vectored vaccines against human and animal diseases must comply with regulatory requirements as they pertain to environmental risk assessment, particularly the characterization of potential adverse effects to humans, animals and the environment. MVA and recombinant MVA are widely believed to pose low or negligible risk to ecosystem health. However, key aspects of MVA biology require further research in order to provide data needed to evaluate the potential risks that may occur due to the use of MVA and MVA-vectored vaccines. The purpose of this paper is to identify knowledge gaps in the biology of MVA and recombinant MVA that are of relevance to its hazard characterization and discuss ongoing and future experiments aimed at providing data necessary to fill in the knowledge gaps. In addition, we presented arguments for the inclusion of uncertainty analysis and experimental investigation of verifiable worst-case scenarios in the environmental risk assessment of MVA and recombinant MVA. These will contribute to improved risk assessment of MVA and recombinant MVA vaccines. Full article

(This article belongs to the Special Issue Smallpox and Emerging Zoonotic Orthopoxviruses: What Is Coming Next?)

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21 pages, 3713 KiB

Open AccessReview

Hijacking of the Ubiquitin/Proteasome Pathway by the HIV Auxiliary Proteins

by Tanja Seissler, Roland Marquet

and Jean-Christophe Paillart^*

Université de Strasbourg, CNRS, Architecture et Réactivité de l’ARN, UPR 9002, IBMC-15 rue René Descartes, F-67000 Strasbourg, France

Viruses 2017, 9(11), 322; https://doi.org/10.3390/v9110322 - 31 Oct 2017

Cited by 56 | Viewed by 14490

Abstract

The ubiquitin-proteasome system (UPS) ensures regulation of the protein pool in the cell by ubiquitination of proteins followed by their degradation by the proteasome. It plays a central role in the cell under normal physiological conditions as well as during viral infections. On [...] Read more.

The ubiquitin-proteasome system (UPS) ensures regulation of the protein pool in the cell by ubiquitination of proteins followed by their degradation by the proteasome. It plays a central role in the cell under normal physiological conditions as well as during viral infections. On the one hand, the UPS can be used by the cell to degrade viral proteins, thereby restricting the viral infection. On the other hand, it can also be subverted by the virus to its own advantage, notably to induce degradation of cellular restriction factors. This makes the UPS a central player in viral restriction and counter-restriction. In this respect, the human immunodeficiency viruses (HIV-1 and 2) represent excellent examples. Indeed, many steps of the HIV life cycle are restricted by cellular proteins, some of which are themselves components of the UPS. However, HIV itself hijacks the UPS to mediate defense against several cellular restriction factors. For example, the HIV auxiliary proteins Vif, Vpx and Vpu counteract specific restriction factors by the recruitment of cellular UPS components. In this review, we describe the interplay between HIV and the UPS to illustrate its role in the restriction of viral infections and its hijacking by viral proteins for counter-restriction. Full article

(This article belongs to the Special Issue Viruses, ERAD, and the Proteasome)

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11 pages, 813 KiB

Open AccessReview

Protoparvovirus Interactions with the Cellular DNA Damage Response

by Kinjal Majumder, Igor Etingov and David J. Pintel^*

Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Bond Life Sciences Center, Columbia, MO 65211, USA

Viruses 2017, 9(11), 323; https://doi.org/10.3390/v9110323 - 31 Oct 2017

Cited by 20 | Viewed by 6057

Abstract

Protoparvoviruses are simple single-stranded DNA viruses that infect many animal species. The protoparvovirus minute virus of mice (MVM) infects murine and transformed human cells provoking a sustained DNA damage response (DDR). This DDR is dependent on signaling by the ATM kinase and leads [...] Read more.

Protoparvoviruses are simple single-stranded DNA viruses that infect many animal species. The protoparvovirus minute virus of mice (MVM) infects murine and transformed human cells provoking a sustained DNA damage response (DDR). This DDR is dependent on signaling by the ATM kinase and leads to a prolonged pre-mitotic cell cycle block that features the inactivation of ATR-kinase mediated signaling, proteasome-targeted degradation of p21, and inhibition of cyclin B1 expression. This review explores how protoparvoviruses, and specifically MVM, co-opt the common mechanisms regulating the DDR and cell cycle progression in order to prepare the host nuclear environment for productive infection. Full article

(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)

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17 pages, 1090 KiB

Open AccessReview

Clinical Relevance of Total HIV DNA in Peripheral Blood Mononuclear Cell Compartments as a Biomarker of HIV-Associated Neurocognitive Disorders (HAND)

by Vurayai Ruhanya^1,2,*, Graeme B. Jacobs¹

, Richard H. Glashoff^3,4 and Susan Engelbrecht^1,5,*

¹ Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Avenue, P.O. Box 241, Cape Town 8000, South Africa

² Department of Medical Microbiology, College of Health Sciences, University of Zimbabwe, P.O. Box A178, Avondale Harare 00263, Zimbabwe

³ Division of Medical Microbiology and Immunology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Avenue, P.O. Box 241, Cape Town 8000, South Africa

⁴ Division of Medical Microbiology and Immunology, National Health Laboratory Service (NHLS), Tygerberg Business Unit, P.O. Box 241, Cape Town 8000, South Africa

⁵ Division of Medical Virology, National Health Laboratory Service (NHLS), Tygerberg Business Unit, P.O. Box 241, Cape Town 8000, South Africa

Viruses 2017, 9(11), 324; https://doi.org/10.3390/v9110324 - 31 Oct 2017

Cited by 18 | Viewed by 9642

Abstract

The pathogenesis of HIV-associated neurocognitive disorders is complex and multifactorial. It is hypothesized that the critical events initiating this condition occur outside the brain, particularly in the peripheral blood. Diagnoses of HIV-induced neurocognitive disorders largely rely on neuropsychometric assessments, which are not precise. [...] Read more.

The pathogenesis of HIV-associated neurocognitive disorders is complex and multifactorial. It is hypothesized that the critical events initiating this condition occur outside the brain, particularly in the peripheral blood. Diagnoses of HIV-induced neurocognitive disorders largely rely on neuropsychometric assessments, which are not precise. Total HIV DNA in the peripheral blood mononuclear cells (PBMCs), quantified by PCR, correlate with disease progression, which is a promising biomarker to predict HAND. Numerous PCR assays for HIV DNA in cell compartments are prone to variation due to the lack of standardization and, therefore, their utility in predicting HAND produced different outcomes. This review evaluates the clinical relevance of total HIV DNA in circulating mononuclear cells using different published quantitative PCR (qPCR) protocols. The rationale is to shed light on the most appropriate assays and sample types used to accurately quantify HIV DNA load, which predicts severity of neurocognitive impairment. The role of monocytes as a vehicle for trafficking HIV into the CNS makes it the most suitable sample for determining a HAND associated reservoir. Studies have also shown significant associations between monocyte HIV DNA levels with markers of neurodamage. However, qPCR assays using PBMCs are cheaper and available commercially, thus could be beneficial in clinical settings. There is need, however, to standardise DNA extraction, normalisation and limit of detection. Full article

(This article belongs to the Section Animal Viruses)

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18 pages, 2187 KiB

Open AccessReview

Biology of the BKPyV: An Update

by Francois Helle^*

, Etienne Brochot, Lynda Handala, Elodie Martin

, Sandrine Castelain, Catherine Francois and Gilles Duverlie

EA4294, Unité de Virologie Clinique et Fondamentale, Centre Universitaire de Recherche en Santé, Centre Hospitalier Universitaire et Université de Picardie Jules Verne, 80054 Amiens, France

Viruses 2017, 9(11), 327; https://doi.org/10.3390/v9110327 - 3 Nov 2017

Cited by 83 | Viewed by 14581

Abstract

The BK virus (BKPyV) is a member of the Polyomaviridae family first isolated in 1971. BKPyV causes frequent infections during childhood and establishes persistent infections with minimal clinical implications within renal tubular cells and the urothelium. However, reactivation of BKPyV in immunocompromised individuals [...] Read more.

The BK virus (BKPyV) is a member of the Polyomaviridae family first isolated in 1971. BKPyV causes frequent infections during childhood and establishes persistent infections with minimal clinical implications within renal tubular cells and the urothelium. However, reactivation of BKPyV in immunocompromised individuals may cause serious complications. In particular, with the implementation of more potent immunosuppressive drugs in the last decade, BKPyV has become an emerging pathogen in kidney and bone marrow transplant recipients where it often causes associated nephropathy and haemorrhagic cystitis, respectively. Unfortunately, no specific antiviral against BKPyV has been approved yet and the only therapeutic option is a modulation of the immunosuppressive drug regimen to improve immune control though it may increase the risk of rejection. A better understanding of the BKPyV life cycle is thus needed to develop efficient treatment against this virus. In this review, we provide an update on recent advances in understanding the biology of BKPyV. Full article

(This article belongs to the Section Animal Viruses)

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12 pages, 3322 KiB

Open AccessReview

Structure and Function of Caliciviral RNA Polymerases

by Ji-Hye Lee¹, Mi Sook Chung² and Kyung Hyun Kim^1,*

¹ Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Korea

² Department of Food and Nutrition, Duksung Women’s University, Seoul 01369, Korea

Viruses 2017, 9(11), 329; https://doi.org/10.3390/v9110329 - 6 Nov 2017

Cited by 14 | Viewed by 7347

Abstract

Caliciviruses are a leading agent of human and animal gastroenteritis and respiratory tract infections, which are growing concerns in immunocompromised individuals. However, no vaccines or therapeutics are yet available. Since the rapid rate of genetic evolution of caliciviruses is mainly due to the [...] Read more.

Caliciviruses are a leading agent of human and animal gastroenteritis and respiratory tract infections, which are growing concerns in immunocompromised individuals. However, no vaccines or therapeutics are yet available. Since the rapid rate of genetic evolution of caliciviruses is mainly due to the error-prone nature of RNA-dependent RNA polymerase (RdRp), this article focuses on recent studies of the structures and functions of RdRp from caliciviruses. It also provides recent advances in the interactions of RdRp with virion protein genome-linked (VPg) and RNA and the structural and functional features of its precursor. Full article

(This article belongs to the Special Issue Structure-Function Relationships in Viral Polymerases)

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17 pages, 5767 KiB

Open AccessReview

Poxvirus Host Range Genes and Virus–Host Spectrum: A Critical Review

by Graziele Pereira Oliveira^†, Rodrigo Araújo Lima Rodrigues^†, Maurício Teixeira Lima^†, Betânia Paiva Drumond and Jônatas Santos Abrahão^*

¹ Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil

^† These authors contributed equally to this work.

Viruses 2017, 9(11), 331; https://doi.org/10.3390/v9110331 - 7 Nov 2017

Cited by 89 | Viewed by 11787

Abstract

The Poxviridae family is comprised of double-stranded DNA viruses belonging to nucleocytoplasmic large DNA viruses (NCLDV). Among the NCLDV, poxviruses exhibit the widest known host range, which is likely observed because this viral family has been more heavily investigated. However, relative to each [...] Read more.

The Poxviridae family is comprised of double-stranded DNA viruses belonging to nucleocytoplasmic large DNA viruses (NCLDV). Among the NCLDV, poxviruses exhibit the widest known host range, which is likely observed because this viral family has been more heavily investigated. However, relative to each member of the Poxviridae family, the spectrum of the host is variable, where certain viruses can infect a large range of hosts, while others are restricted to only one host species. It has been suggested that the variability in host spectrum among poxviruses is linked with the presence or absence of some host range genes. Would it be possible to extrapolate the restriction of viral replication in a specific cell lineage to an animal, a far more complex organism? In this study, we compare and discuss the relationship between the host range of poxvirus species and the abundance/diversity of host range genes. We analyzed the sequences of 38 previously identified and putative homologs of poxvirus host range genes, and updated these data with deposited sequences of new poxvirus genomes. Overall, the term host range genes might not be the most appropriate for these genes, since no correlation between them and the viruses’ host spectrum was observed, and a change in nomenclature should be considered. Finally, we analyzed the evolutionary history of these genes, and reaffirmed the occurrence of horizontal gene transfer (HGT) for certain elements, as previously suggested. Considering the data presented in this study, it is not possible to associate the diversity of host range factors with the amount of hosts of known poxviruses, and this traditional nomenclature creates misunderstandings. Full article

(This article belongs to the Special Issue Smallpox and Emerging Zoonotic Orthopoxviruses: What Is Coming Next?)

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14 pages, 4162 KiB

Open AccessReview

Structures and Functions of the Envelope Glycoprotein in Flavivirus Infections

by Xingcui Zhang^1,2, Renyong Jia^1,2,3,*, Haoyue Shen^1,2, Mingshu Wang^1,2,3, Zhongqiong Yin³ and Anchun Cheng^1,2,3,*

¹ Research Center of Avian Disease, College of Veterinary Medicine of Sichuan Agricultural University, Wenjiang District, Chengdu 611130, China

² Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang District, Chengdu 611130, China

³ Key Laboratory of Animal Disease and Human Health of Sichuan Province, Wenjiang District, Chengdu 611130, China

Viruses 2017, 9(11), 338; https://doi.org/10.3390/v9110338 - 13 Nov 2017

Cited by 140 | Viewed by 14590

Abstract

Flaviviruses are enveloped, single-stranded RNA viruses that widely infect many animal species. The envelope protein, a structural protein of flavivirus, plays an important role in host cell viral infections. It is composed of three separate structural envelope domains I, II, and III (EDI, [...] Read more.

Flaviviruses are enveloped, single-stranded RNA viruses that widely infect many animal species. The envelope protein, a structural protein of flavivirus, plays an important role in host cell viral infections. It is composed of three separate structural envelope domains I, II, and III (EDI, EDII, and EDIII). EDI is a structurally central domain of the envelope protein which stabilizes the overall orientation of the protein, and the glycosylation sites in EDI are related to virus production, pH sensitivity, and neuroinvasiveness. EDII plays an important role in membrane fusion because of the immunodominance of the fusion loop epitope and the envelope dimer epitope. Additionally, EDIII is the major target of neutralization antibodies. The envelope protein is an important target for research to develop vaccine candidates and antiviral therapeutics. This review summarizes the structures and functions of ED I/II/III, and provides practical applications for the three domains, with the ultimate goal of implementing strategies to utilize the envelope protein against flavivirus infections, thus achieving better diagnostics and developing potential flavivirus therapeutics and vaccines. Full article

(This article belongs to the Collection Advances in Ebolavirus, Marburgvirus, and Cuevavirus Research)

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34 pages, 1344 KiB

Open AccessReview

EBV and Apoptosis: The Viral Master Regulator of Cell Fate?

by Leah Fitzsimmons¹

and Gemma L. Kelly^2,3,*

¹ Institute of Cancer and Genomic Sciences and Centre for Human Virology, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK

² Molecular Genetics of Cancer Division, The Walter and Eliza Hall Institute for Medical Research, Parkville, Melbourne, VIC 3052, Australia

³ Department of Medical Biology, The University of Melbourne, Parkville, Melbourne, VIC 3052, Australia

Viruses 2017, 9(11), 339; https://doi.org/10.3390/v9110339 - 13 Nov 2017

Cited by 67 | Viewed by 12615

Abstract

Epstein–Barr virus (EBV) was first discovered in cells from a patient with Burkitt lymphoma (BL), and is now known to be a contributory factor in 1–2% of all cancers, for which there are as yet, no EBV-targeted therapies available. Like other herpesviruses, EBV [...] Read more.

Epstein–Barr virus (EBV) was first discovered in cells from a patient with Burkitt lymphoma (BL), and is now known to be a contributory factor in 1–2% of all cancers, for which there are as yet, no EBV-targeted therapies available. Like other herpesviruses, EBV adopts a persistent latent infection in vivo and only rarely reactivates into replicative lytic cycle. Although latency is associated with restricted patterns of gene expression, genes are never expressed in isolation; always in groups. Here, we discuss (1) the ways in which the latent genes of EBV are known to modulate cell death, (2) how these mechanisms relate to growth transformation and lymphomagenesis, and (3) how EBV genes cooperate to coordinately regulate key cell death pathways in BL and lymphoblastoid cell lines (LCLs). Since manipulation of the cell death machinery is critical in EBV pathogenesis, understanding the mechanisms that underpin EBV regulation of apoptosis therefore provides opportunities for novel therapeutic interventions. Full article

(This article belongs to the Special Issue Viral Infection and Apoptosis)

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21 pages, 2773 KiB

Open AccessReview

Vaccinia Virus Natural Infections in Brazil: The Good, the Bad, and the Ugly

by Jaqueline Silva de Oliveira^1,†, Poliana De Oliveira Figueiredo^1,†, Galileu Barbosa Costa^1,*,†

, Felipe Lopes de Assis², Betânia Paiva Drumond¹, Flávio Guimarães Da Fonseca³

, Maurício Lacerda Nogueira⁴

, Erna Geessien Kroon¹

and Giliane De Souza Trindade^1,*

¹ Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil

² United States Food and Drug Administration, Silver Spring, MD 20993-0002, USA

³ Laboratório de Virologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil

⁴ Laboratório de Pesquisas em Virologia, Departamento de Doenças Infecciosas e Parasitárias, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, São Paulo 15090-000, Brazil

^† These authors contributed equally to this work.

Viruses 2017, 9(11), 340; https://doi.org/10.3390/v9110340 - 15 Nov 2017

Cited by 42 | Viewed by 9617

Abstract

The orthopoxviruses (OPV) comprise several emerging viruses with great importance to human and veterinary medicine, including vaccinia virus (VACV), which causes outbreaks of bovine vaccinia (BV) in South America. Historically, VACV is the most comprehensively studied virus, however, its origin and natural hosts [...] Read more.

The orthopoxviruses (OPV) comprise several emerging viruses with great importance to human and veterinary medicine, including vaccinia virus (VACV), which causes outbreaks of bovine vaccinia (BV) in South America. Historically, VACV is the most comprehensively studied virus, however, its origin and natural hosts remain unknown. VACV was the primary component of the smallpox vaccine, largely used during the smallpox eradication campaign. After smallpox was declared eradicated, the vaccination that conferred immunity to OPV was discontinued, favoring a new contingent of susceptible individuals to OPV. VACV infections occur naturally after direct contact with infected dairy cattle, in recently vaccinated individuals, or through alternative routes of exposure. In Brazil, VACV outbreaks are frequently reported in rural areas, affecting mainly farm animals and humans. Recent studies have shown the role of wildlife in the VACV transmission chain, exploring the role of wild rodents as reservoirs that facilitate VACV spread throughout rural areas. Furthermore, VACV circulation in urban environments and the significance of this with respect to public health, have also been explored. In this review, we discuss the history, epidemiological, ecological and clinical aspects of natural VACV infections in Brazil, also highlighting alternative routes of VACV transmission, the factors involved in susceptibility to infection, and the natural history of the disease in humans and animals, and the potential for dissemination to urban environments. Full article

(This article belongs to the Special Issue Smallpox and Emerging Zoonotic Orthopoxviruses: What Is Coming Next?)

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16 pages, 1031 KiB

Open AccessReview

Epstein–Barr Virus Hijacks DNA Damage Response Transducers to Orchestrate Its Life Cycle

by Pok Man Hau^1,* and Sai Wah Tsao²

¹ Department of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

² School of Biomedical Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

Viruses 2017, 9(11), 341; https://doi.org/10.3390/v9110341 - 16 Nov 2017

Cited by 47 | Viewed by 9469

Abstract

The Epstein–Barr virus (EBV) is a ubiquitous virus that infects most of the human population. EBV infection is associated with multiple human cancers, including Burkitt’s lymphoma, Hodgkin’s lymphoma, a subset of gastric carcinomas, and almost all undifferentiated non-keratinizing nasopharyngeal carcinoma. Intensive research has [...] Read more.

The Epstein–Barr virus (EBV) is a ubiquitous virus that infects most of the human population. EBV infection is associated with multiple human cancers, including Burkitt’s lymphoma, Hodgkin’s lymphoma, a subset of gastric carcinomas, and almost all undifferentiated non-keratinizing nasopharyngeal carcinoma. Intensive research has shown that EBV triggers a DNA damage response (DDR) during primary infection and lytic reactivation. The EBV-encoded viral proteins have been implicated in deregulating the DDR signaling pathways. The consequences of DDR inactivation lead to genomic instability and promote cellular transformation. This review summarizes the current understanding of the relationship between EBV infection and the DDR transducers, including ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related), and DNA-PK (DNA-dependent protein kinase), and discusses how EBV manipulates the DDR signaling pathways to complete the replication process of viral DNA during lytic reactivation. Full article

(This article belongs to the Special Issue Viruses and the DNA Damage Response)

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14 pages, 929 KiB

Open AccessReview

Epigenetic Regulation of Viral Biological Processes

by Lata Balakrishnan¹

and Barry Milavetz^2,*

¹ Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA

² Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA

Viruses 2017, 9(11), 346; https://doi.org/10.3390/v9110346 - 17 Nov 2017

Cited by 48 | Viewed by 10359

Abstract

It is increasingly clear that DNA viruses exploit cellular epigenetic processes to control their life cycles during infection. This review will address epigenetic regulation in members of the polyomaviruses, adenoviruses, human papillomaviruses, hepatitis B, and herpes viruses. For each type of virus, what [...] Read more.

It is increasingly clear that DNA viruses exploit cellular epigenetic processes to control their life cycles during infection. This review will address epigenetic regulation in members of the polyomaviruses, adenoviruses, human papillomaviruses, hepatitis B, and herpes viruses. For each type of virus, what is known about the roles of DNA methylation, histone modifications, nucleosome positioning, and regulatory RNA in epigenetic regulation of the virus infection will be discussed. The mechanisms used by certain viruses to dysregulate the host cell through manipulation of epigenetic processes and the role of cellular cofactors such as BRD4 that are known to be involved in epigenetic regulation of host cell pathways will also be covered. Specifically, this review will focus on the role of epigenetic regulation in maintaining viral episomes through the generation of chromatin, temporally controlling transcription from viral genes during the course of an infection, regulating latency and the switch to a lytic infection, and global dysregulation of cellular function. Full article

(This article belongs to the Special Issue Viral Subversion of Transcriptional Control)

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23 pages, 2848 KiB

Open AccessReview

New Paradigms for the Study of Ocular Alphaherpesvirus Infections: Insights into the Use of Non-Traditional Host Model Systems

by Matthew R. Pennington¹

, Eric C. Ledbetter² and Gerlinde R. Van de Walle^1,*

¹ Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA

² Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA

Viruses 2017, 9(11), 349; https://doi.org/10.3390/v9110349 - 18 Nov 2017

Cited by 15 | Viewed by 9037

Abstract

Ocular herpesviruses, most notably human alphaherpesvirus 1 (HSV-1), canid alphaherpesvirus 1 (CHV-1) and felid alphaherpesvirus 1 (FHV-1), infect and cause severe disease that may lead to blindness. CHV-1 and FHV-1 have a pathogenesis and induce clinical disease in their hosts that is similar [...] Read more.

Ocular herpesviruses, most notably human alphaherpesvirus 1 (HSV-1), canid alphaherpesvirus 1 (CHV-1) and felid alphaherpesvirus 1 (FHV-1), infect and cause severe disease that may lead to blindness. CHV-1 and FHV-1 have a pathogenesis and induce clinical disease in their hosts that is similar to HSV-1 ocular infections in humans, suggesting that infection of dogs and cats with CHV-1 and FHV-1, respectively, can be used as a comparative natural host model of herpesvirus-induced ocular disease. In this review, we discuss both strengths and limitations of the various available model systems to study ocular herpesvirus infection, with a focus on the use of these non-traditional virus-natural host models. Recent work has demonstrated the robustness and reproducibility of experimental ocular herpesvirus infections in dogs and cats, and, therefore, these non-traditional models can provide additional insights into the pathogenesis of ocular herpesvirus infections. Full article

(This article belongs to the Section Animal Viruses)

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16 pages, 2336 KiB

Open AccessReview

Therapeutic Strategies against Epstein-Barr Virus-Associated Cancers Using Proteasome Inhibitors

by Kwai Fung Hui^1,2,†, Kam Pui Tam^1,2,† and Alan Kwok Shing Chiang^1,2,*

¹ Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China

² Center for Nasopharyngeal Carcinoma Research, The University of Hong Kong, Hong Kong, China

^† These authors contributed equally to this work.

Viruses 2017, 9(11), 352; https://doi.org/10.3390/v9110352 - 21 Nov 2017

Cited by 17 | Viewed by 7359

Abstract

Epstein-Barr virus (EBV) is closely associated with several lymphomas (endemic Burkitt lymphoma, Hodgkin lymphoma and nasal NK/T-cell lymphoma) and epithelial cancers (nasopharyngeal carcinoma and gastric carcinoma). To maintain its persistence in the host cells, the virus manipulates the ubiquitin-proteasome system to regulate viral [...] Read more.

Epstein-Barr virus (EBV) is closely associated with several lymphomas (endemic Burkitt lymphoma, Hodgkin lymphoma and nasal NK/T-cell lymphoma) and epithelial cancers (nasopharyngeal carcinoma and gastric carcinoma). To maintain its persistence in the host cells, the virus manipulates the ubiquitin-proteasome system to regulate viral lytic reactivation, modify cell cycle checkpoints, prevent apoptosis and evade immune surveillance. In this review, we aim to provide an overview of the mechanisms by which the virus manipulates the ubiquitin-proteasome system in EBV-associated lymphoid and epithelial malignancies, to evaluate the efficacy of proteasome inhibitors on the treatment of these cancers and discuss potential novel viral-targeted treatment strategies against the EBV-associated cancers. Full article

(This article belongs to the Special Issue Viruses, ERAD, and the Proteasome)

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13 pages, 1567 KiB

Open AccessReview

Human Protoparvoviruses

by Elina Väisänen¹, Yu Fu¹, Klaus Hedman^1,2 and Maria Söderlund-Venermo^1,*

¹ Department of Virology, University of Helsinki, Helsinki 00290, Finland

² Helsinki University Hospital, Helsinki 00290, Finland

Viruses 2017, 9(11), 354; https://doi.org/10.3390/v9110354 - 22 Nov 2017

Cited by 40 | Viewed by 6152

Abstract

Next-generation sequencing and metagenomics have revolutionized the discovery of novel viruses. In recent years, three novel protoparvoviruses have been discovered in fecal samples of humans: bufavirus (BuV) in 2012, tusavirus (TuV) in 2014, and cutavirus (CuV) in 2016. BuV has since been studied [...] Read more.

Next-generation sequencing and metagenomics have revolutionized the discovery of novel viruses. In recent years, three novel protoparvoviruses have been discovered in fecal samples of humans: bufavirus (BuV) in 2012, tusavirus (TuV) in 2014, and cutavirus (CuV) in 2016. BuV has since been studied the most, disclosing three genotypes that also represent serotypes. Besides one nasal sample, BuV DNA has been found exclusively in diarrheal feces, but not in non-diarrheal feces, suggesting a causal relationship. According to both geno- and seroprevalences, BuV appears to be the most common of the three novel protoparvoviruses, whereas TuV DNA has been found in only a single fecal sample, with antibody detection being equally rare. Moreover, the TuV sequence is closer to those of non-human protoparvoviruses, and so the evidence of TuV being a human virus is thus far insufficient. Interestingly, besides in feces, CuV has also been detected in skin biopsies of patients with cutaneous T-cell lymphoma and a patient with melanoma, while all other skin samples have tested PCR negative. Even if preliminary disease associations exist, the full etiological roles of these viruses in human disease are yet to be resolved. Full article

(This article belongs to the Special Issue Protoparvoviruses: Friends or Foes?)

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8 pages, 515 KiB

Open AccessPerspective

The Role of Brincidofovir in Preparation for a Potential Smallpox Outbreak

by Scott A. Foster^1,*, Scott Parker²

and Randall Lanier¹

¹ Chimerix, Durham, NC 27713, USA

² Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA

Viruses 2017, 9(11), 320; https://doi.org/10.3390/v9110320 - 30 Oct 2017

Cited by 24 | Viewed by 6662

Abstract

Smallpox (variola) virus is considered a Category A bioterrorism agent due to its ability to spread rapidly and the high morbidity and mortality rates associated with infection. Current recommendations recognize the importance of oral antivirals and call for having at least two smallpox [...] Read more.

Smallpox (variola) virus is considered a Category A bioterrorism agent due to its ability to spread rapidly and the high morbidity and mortality rates associated with infection. Current recommendations recognize the importance of oral antivirals and call for having at least two smallpox antivirals with different mechanisms of action available in the event of a smallpox outbreak. Multiple antivirals are recommended due in large part to the propensity of viruses to become resistant to antiviral therapy, especially monotherapy. Advances in synthetic biology heighten concerns that a bioterror attack with variola would utilize engineered resistance to antivirals and potentially vaccines. Brincidofovir, an oral antiviral in late stage development, has proven effective against orthopoxviruses in vitro and in vivo, has a different mechanism of action from tecovirimat (the only oral smallpox antiviral currently in the US Strategic National Stockpile), and has a resistance profile that reduces concerns in the scenario of a bioterror attack using genetically engineered smallpox. Given the devastating potential of smallpox as a bioweapon, preparation of a multi-pronged defense that accounts for the most obvious bioengineering possibilities is strategically imperative. Full article

(This article belongs to the Special Issue Smallpox and Emerging Zoonotic Orthopoxviruses: What Is Coming Next?)

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26 pages, 1066 KiB

Open AccessConference Report

The 17th Rocky Mountain Virology Association Meeting

by Joel Rovnak¹

, Rushika Perera², Matthew W. Hopken^1,3, Jenna Read², Derrick M. Waller⁴

and Randall J. Cohrs^5,*

¹ Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA

² Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA

³ USDA-APHIS National Wildlife Research Center, Fort Collins, CO 80521, USA

⁴ Department of Pharmaceutical Sciences, Regis University School of Pharmacy, Denver, CO 80221, USA

⁵ Departments of Neurology and Immunology/Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA

Viruses 2017, 9(11), 333; https://doi.org/10.3390/v9110333 - 8 Nov 2017

Viewed by 5768

Abstract

Since 2000, scientists and students from the greater Rocky Mountain region, along with invited speakers, both national and international, have gathered at the Mountain Campus of Colorado State University to discuss their area of study, present recent findings, establish or strengthen collaborations, and [...] Read more.

Since 2000, scientists and students from the greater Rocky Mountain region, along with invited speakers, both national and international, have gathered at the Mountain Campus of Colorado State University to discuss their area of study, present recent findings, establish or strengthen collaborations, and mentor the next generation of virologists and prionologists through formal presentations and informal discussions concerning science, grantsmanship and network development. This year, approximately 100 people attended the 17th annual Rocky Mountain Virology Association meeting, that began with a keynote presentation, and featured 29 oral and 35 poster presentations covering RNA and DNA viruses, prions, virus-host interactions and guides to successful mentorship. Since the keynote address focused on the structure and function of Zika and related flaviviruses, a special session was held to discuss RNA control. The secluded meeting at the foot of the Colorado Rocky Mountains gave ample time for in-depth discussions amid the peak of fall colors in the aspen groves while the random bear provided excitement. On behalf of the Rocky Mountain Virology Association, this report summarizes the >50 reports. Full article

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