Viruses

11 pages, 5332 KiB

Open AccessArticle

Identification and Application of Neutralizing Epitopes of Human Adenovirus Type 55 Hexon Protein

by Xingui Tian^1,†, Qiang Ma^1,2,†, Zaixue Jiang², Junfeng Huang³, Qian Liu², Xiaomei Lu², Qingming Luo^2,* and Rong Zhou^1,*

¹ State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510230, China

² Dongguan Institute of Pediatrics, Dongguan Children’s Hospital, Dongguan 523325, China

³ School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China

^† These authors contributed equally to this work.

Viruses 2015, 7(10), 5632-5642; https://doi.org/10.3390/v7102896 - 27 Oct 2015

Cited by 16 | Viewed by 6648

Abstract

Human adenovirus type 55 (HAdV55) is a newly identified re-emergent acute respiratory disease (ARD) pathogen with a proposed recombination of hexon gene between HAdV11 and HAdV14 strains. The identification of the neutralizing epitopes is important for the surveillance and vaccine development against HAdV55 [...] Read more.

Human adenovirus type 55 (HAdV55) is a newly identified re-emergent acute respiratory disease (ARD) pathogen with a proposed recombination of hexon gene between HAdV11 and HAdV14 strains. The identification of the neutralizing epitopes is important for the surveillance and vaccine development against HAdV55 infection. In this study, four type-specific epitope peptides of HAdV55 hexon protein, A55R1 (residues 138 to 152), A55R2 (residues 179 to 187), A55R4 (residues 247 to 259) and A55R7 (residues 429 to 443), were predicted by multiple sequence alignment and homology modeling methods, and then confirmed with synthetic peptides by enzyme-linked immunosorbent assay (ELISA) and neutralization tests (NT). Finally, the A55R2 was incorporated into human adenoviruses 3 (HAdV3) and a chimeric adenovirus rAd3A55R2 was successfully obtained. The chimeric rAd3A55R2 could induce neutralizing antibodies against both HAdV3 and HAdV55. This current study will contribute to the development of novel adenovirus vaccine candidate and adenovirus structural analysis. Full article

(This article belongs to the Section Animal Viruses)

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13 pages, 2057 KiB

Open AccessArticle

Exposure to West Nile Virus Increases Bacterial Diversity and Immune Gene Expression in Culex pipiens

by Steven D. Zink¹, Greta A. Van Slyke¹, Michael J. Palumbo², Laura D. Kramer¹ and Alexander T. Ciota^1,*

¹ Griffin Laboratory, Wadsworth Center, New York State Department of Health, Slingerlands, NY 12159, USA

² Wadsworth Center Bioinformatics Core, Wadsworth Center, New York State Department of Health, Albany, NY 12222, USA

Viruses 2015, 7(10), 5619-5631; https://doi.org/10.3390/v7102886 - 27 Oct 2015

Cited by 40 | Viewed by 7084

Abstract

Complex interactions between microbial residents of mosquitoes and arboviruses are likely to influence many aspects of vectorial capacity and could potentially have profound effects on patterns of arbovirus transmission. Such interactions have not been well studied for West Nile virus (WNV; Flaviviridae, Flavivirus [...] Read more.

Complex interactions between microbial residents of mosquitoes and arboviruses are likely to influence many aspects of vectorial capacity and could potentially have profound effects on patterns of arbovirus transmission. Such interactions have not been well studied for West Nile virus (WNV; Flaviviridae, Flavivirus) and Culex spp. mosquitoes. We utilized next-generation sequencing of 16S ribosomal RNA bacterial genes derived from Culex pipiens Linnaeus following WNV exposure and/or infection and compared bacterial populations and broad immune responses to unexposed mosquitoes. Our results demonstrate that WNV infection increases the diversity of bacterial populations and is associated with up-regulation of classical invertebrate immune pathways including RNA interference (RNAi), Toll, and Jak-STAT (Janus kinase-Signal Transducer and Activator of Transcription). In addition, WNV exposure alone, without the establishment of infection, results in similar alterations to microbial and immune signatures, although to a lesser extent. Multiple bacterial genera were found in greater abundance inWNV-exposed and/or infected mosquitoes, yet the most consistent and notable was the genus Serratia. Full article

(This article belongs to the Special Issue Impact of the Insect Microbiome on Arbovirus Transmission)

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9 pages, 2029 KiB

Open AccessArticle

Entry of Oncolytic Herpes Simplex Virus into Human Squamous Cell Carcinoma Cells by Ultrasound

by Shusuke Okunaga¹, Ayako Takasu¹, Noritoshi Meshii², Tomoaki Imai¹, Masakagu Hamada¹, Soichi Iwai¹ and Yoshiaki Yura^1,*

¹ Department of Oral and Maxillofacial Surgery, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan

² Dental and Oral Surgery, Izumisano Municipal Hospital, 2-23 Rinkuoraikita, Izumisano, Osaka 598-8577, Japan

Viruses 2015, 7(10), 5610-5618; https://doi.org/10.3390/v7102890 - 26 Oct 2015

Cited by 4 | Viewed by 7301

Abstract

Low-intensity ultrasound is a useful method to introduce materials into cells due to the transient formation of micropores, called sonoporations, on the cell membrane. Whether oncolytic herpes simplex virus type 1 (HSV-1) can be introduced into oral squamous cell carcinoma (SCC) cells through [...] Read more.

Low-intensity ultrasound is a useful method to introduce materials into cells due to the transient formation of micropores, called sonoporations, on the cell membrane. Whether oncolytic herpes simplex virus type 1 (HSV-1) can be introduced into oral squamous cell carcinoma (SCC) cells through membrane pores remains undetermined. Human SCC cell line SAS and oncolytic HSV-1 RH2, which was deficient in the 134.5 gene and fusogenic, were used. Cells were exposed to ultrasound in the presence or absence of microbubbles. The increase of virus entry was estimated by plaque numbers. Viral infection was hardly established without the adsorption step, but plaque number was increased by the exposure of HSV-1-inoculated cells to ultrasound. Plaque number was also increased even if SAS cells were exposed to ultrasound and inoculated with RH2 without the adsorption step. This effect was abolished when the interval from ultrasound exposure to virus inoculation was prolonged. Scanning electron microscopy revealed depressed spots on the cell surface after exposure to ultrasound. These results suggest that oncolytic HSV-1 RH2 can be introduced into SAS cells through ultrasound-mediated pores of the cell membrane that are resealed after an interval. Full article

(This article belongs to the Special Issue Oncolytic Viruses)

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1 pages, 150 KiB

Open AccessAddendum

Addendum: Kong, M.Y.; Whitley, R.J.; Peng, N.; Oster, R.; Schoeb, T.R.; Sullender, W.; Ambalavanan, N.; Clancy, J.P.; Gaggar, A.; Blalock J.E. Matrix Metalloproteinase-9 Mediates RSV Infection in Vitro and in Vivo. Viruses 2015, 30, 7, 4230–4253

by Michele Y. F. Kong^1,*, Richard J. Whitley¹, Ning Peng¹, Robert Oster²

, Trenton R. Schoeb³, Wayne Sullender⁴, Namasivayam Ambalavanan¹, John Paul Clancy⁵, Amit Gaggar^2,† and J. Edwin Blalock^2,†

¹ Departments of Pediatrics, University of Alabama at Birmingham, PPS 102, 1600 5th Ave South, Birmingham, AL 35233, USA

² Departments of Medicine, University of Alabama at Birmingham, PPS 102, 1600 5th Ave South, Birmingham, AL 35233, USA

³ Departments of Genetics, University of Alabama at Birmingham, PPS 102, 1600 5th Ave South, Birmingham, AL 35233, USA

⁴ Center for Global Health, Colorado School of Public Health, 13199 E Montview Blvd, Suite 310, A090 Aurora, CO 80045, USA

⁵ Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA

^† These authors contributed equally to this work.

Viruses 2015, 7(10), 5609; https://doi.org/10.3390/v7102889 - 26 Oct 2015

Cited by 2 | Viewed by 4394

Abstract

The authors wish to make the following addition to their paper [1]. [...] Full article

6 pages, 170 KiB

Open AccessEditorial

Special Issue: Honey Bee Viruses

by Sebastian Gisder^* and Elke Genersch

Institute for Bee Research, Department of Molecular Microbiology and Bee Diseases, Friedrich-Engels-Str. 32, 16540 Hohen Neuendorf, Germany

Viruses 2015, 7(10), 5603-5608; https://doi.org/10.3390/v7102885 - 26 Oct 2015

Cited by 25 | Viewed by 9510

Abstract

Pollination of flowering plants is an important ecosystem service provided by wild insect pollinators and managed honey bees. Hence, losses and declines of pollinating insect species threaten human food security and are of major concern not only for apiculture or agriculture but for [...] Read more.

Pollination of flowering plants is an important ecosystem service provided by wild insect pollinators and managed honey bees. Hence, losses and declines of pollinating insect species threaten human food security and are of major concern not only for apiculture or agriculture but for human society in general. Honey bee colony losses and bumblebee declines have attracted intensive research interest over the last decade and although the problem is far from being solved we now know that viruses are among the key players of many of these bee losses and bumblebee declines. With this special issue on bee viruses we, therefore, aimed to collect high quality original papers reflecting the current state of bee virus research. To this end, we focused on newly discovered viruses (Lake Sinai viruses, bee macula-like virus), or a so far neglected virus species (Apis mellifera filamentous virus), and cutting edge technologies (mass spectrometry, RNAi approach) applied in the field. Full article

(This article belongs to the Special Issue Honeybee Viruses)

16 pages, 5537 KiB

Open AccessArticle

Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism

by Nathan H. Vande Burgt, Rachel L. Kaletsky and Paul Bates^*

Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, 225 Johnson Pavilion, 3610 HamiltonWalk, Philadelphia, PA 19104-6076, USA

Viruses 2015, 7(10), 5587-5602; https://doi.org/10.3390/v7102888 - 26 Oct 2015

Cited by 18 | Viewed by 7410

Abstract

Tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP), to counteract restriction and promote [...] Read more.

Tetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP), to counteract restriction and promote virus release. Unlike other tetherin antagonists such as HIV-1 Vpu or KSHV K5, the features within EboGP needed to overcome tetherin are not well characterized. Here, we describe sequences within the EboGP ectodomain and membrane spanning domain (msd) as necessary to relieve tetherin restriction of viral particle budding. Fusing the EboGP msd to a normally secreted form of the glycoprotein effectively promotes Ebola virus particle release. Cellular protein or lipid anchors could not substitute for the EboGP msd. The requirement for the EboGP msd was not specific for filovirus budding, as similar results were seen with HIV particles. Furthermore trafficking of chimeric proteins to budding sites did not correlate with an ability to counter tetherin. Additionally, we find that a glycoprotein construct, which mimics the cathepsin-activated species by proteolytic removal of the EboGP glycan cap and mucin domains, is unable to counteract tetherin. Combining these results suggests an important role for the EboGP glycan cap and msd in tetherin antagonism. Full article

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

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16 pages, 1586 KiB

Open AccessArticle

Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase

by Xinran Liu¹, Derek M. Musser¹, Cheri A. Lee², Xiaorong Yang¹, Jamie J. Arnold², Craig E. Cameron² and David D. Boehr^1,*

¹ Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA

² Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA

Viruses 2015, 7(10), 5571-5586; https://doi.org/10.3390/v7102894 - 26 Oct 2015

Cited by 4 | Viewed by 5979

Abstract

The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding [...] Read more.

The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation. Full article

(This article belongs to the Special Issue Viral Replication Complexes: Structures, Functions, Applications and Inhibitors)

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18 pages, 1819 KiB

Open AccessArticle

Vector-Enabled Metagenomic (VEM) Surveys Using Whiteflies (Aleyrodidae) Reveal Novel Begomovirus Species in the New and OldWorlds

by Karyna Rosario^1,*, Yee Mey Seah², Christian Marr¹, Arvind Varsani^3,4,5

, Simona Kraberger³, Daisy Stainton³, Enrique Moriones⁶, Jane E. Polston⁴, Siobain Duffy⁷ and Mya Breitbart¹

¹ College of Marine Science, University of South Florida, Saint Petersburg, FL 33701, USA

² Microbiology and Molecular Genetics, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA

³ School of Biological Sciences and Biomolecular Interaction Centre, University of Canterbury, Ilam, Christchurch 8041, New Zealand

⁴ Department of Plant Pathology, University of Florida, Gainesville, FL 32611, USA

⁵ Structural Biology Research Unit, Department of Clinical Laboratory Sciences, University of Cape Town, Rondebosch, Cape Town 7701, South Africa

⁶ Instituto de Hortofruticultura Subtropical y Mediterránea “La Mayora” (IHSM-UMA-CSIC), Consejo Superior de Investigaciones Científicas, Estación Experimental “La Mayora”, Algarrobo-Costa, Málaga 29750, Spain

⁷ Department of Ecology, Evolution and Natural Resources, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA

Viruses 2015, 7(10), 5553-5570; https://doi.org/10.3390/v7102895 - 26 Oct 2015

Cited by 36 | Viewed by 8843

Abstract

Whitefly-transmitted viruses belonging to the genus Begomovirus (family Geminiviridae) represent a substantial threat to agricultural food production. The rapid evolutionary potential of these single-stranded DNA viruses combined with the polyphagous feeding behavior of their whitefly vector (Bemisia tabaci) can lead to the emergence [...] Read more.

Whitefly-transmitted viruses belonging to the genus Begomovirus (family Geminiviridae) represent a substantial threat to agricultural food production. The rapid evolutionary potential of these single-stranded DNA viruses combined with the polyphagous feeding behavior of their whitefly vector (Bemisia tabaci) can lead to the emergence of damaging viral strains. Therefore, it is crucial to characterize begomoviruses circulating in different regions and crops globally. This study utilized vector-enabled metagenomics (VEM) coupled with high-throughput sequencing to survey begomoviruses directly from whiteflies collected in various locations (California (USA), Guatemala, Israel, Puerto Rico, and Spain). Begomoviruses were detected in all locations, with the highest diversity identified in Guatemala where up to seven different species were identified in a single field. Both bipartite and monopartite viruses were detected, including seven new begomovirus species from Guatemala, Puerto Rico, and Spain. This begomovirus survey extends the known diversity of these highly damaging plant viruses. However, the new genomes described here and in the recent literature appear to reflect the outcome of interactions between closely-related species, often resulting from recombination, instead of unique, highly divergent species. Full article

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

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14 pages, 4284 KiB

Open AccessArticle

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2

by Jing Chen^1,2, Xibao Shi^2,3, Xiaozhuan Zhang³, Li Wang², Jun Luo², Guangxu Xing^2,*, Ruiguang Deng², Hong Yang³, Jinting Li³, Aiping Wang⁴ and Gaiping Zhang^1,2,5,*

¹ College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China

² Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China

³ College of Life Sciences, Henan Normal University, Xinxiang 453007, China

⁴ Department of Bioengineering, Zhengzhou University, Zhengzhou 450000, China

⁵ College of Veterinary Medicine and Animal Science, Henan Agricultural University, Zhengzhou 450002, China

Viruses 2015, 7(10), 5539-5552; https://doi.org/10.3390/v7102893 - 23 Oct 2015

Cited by 8 | Viewed by 6920

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) infection strongly modulates the host’s immune response. The RNA silencing pathway is an intracellular innate response to viral infections. However, it is unknown whether PRRSV interacts with cellular RNA silencing to facilitate the viral infection. Here, [...] Read more.

Porcine reproductive and respiratory syndrome virus (PRRSV) infection strongly modulates the host’s immune response. The RNA silencing pathway is an intracellular innate response to viral infections. However, it is unknown whether PRRSV interacts with cellular RNA silencing to facilitate the viral infection. Here, we report for the first time the interaction between PRRSV and RNA silencing in both the porcine macrophages and African green monkey kidney cell line (MARC-145) cell line, which were derived from African green monkey kidney cells and highly permissive for PRRSV infection. Our data demonstrated that PRRSV suppressed RNA silencing induced by short-hairpin (sh) RNA, double-strand (ds) RNA and microRNA (miRNA) and downregulated the expression of argonaute protein-2 (Ago-2), which is a key protein of the RNA silencing pathway in animal cells. Further, exogenous introduction of siRNA and shRNA downregulated Dicer or Ago-2 proteins of the cellular RNA silencing apparatus in MARC-145 cells and porcine macrophages, which, in turn, increased the viral replication and titers. The viral non-structure protein 1α (nsp-1α) and nsp11 of PRRSV were identified as the suppressors for cellular RNA silencing (RSSs) to downregulate the Ago-2 protein. Our results identify that PRRSV, through its nsp proteins, suppresses the cellular RNA silencing apparatus in favor of viral infection and supports a co-evolutionary process of the virus and the cellular RNA silencing process. Full article

(This article belongs to the Section Animal Viruses)

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14 pages, 1728 KiB

Open AccessArticle

Comparative Genomic Analysis of Classical and Variant Virulent Parental/Attenuated Strains of Porcine Epidemic Diarrhea Virus

by Fangzhou Chen, Yinxing Zhu, Meizhou Wu, Xugang Ku, Shiyi Ye, Zhonghua Li, Xiaozhen Guo and Qigai He^*

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China

Viruses 2015, 7(10), 5525-5538; https://doi.org/10.3390/v7102891 - 23 Oct 2015

Cited by 70 | Viewed by 9015

Abstract

Since 2010, the variant porcine epidemic diarrhea virus (PEDV) has been the etiological agent responsible for the outbreak of porcine epidemic diarrhea (PED) worldwide. In this study, a variant PEDV strain YN1 was isolated, serially propagated on the Vero cells and was characterized [...] Read more.

Since 2010, the variant porcine epidemic diarrhea virus (PEDV) has been the etiological agent responsible for the outbreak of porcine epidemic diarrhea (PED) worldwide. In this study, a variant PEDV strain YN1 was isolated, serially propagated on the Vero cells and was characterized for 200 passages. To better elucidate the molecular basis of Vero cell adaptation of variant PEDV strains, we sequenced, compared, and analyzed the full-genome sequences of parental YN1 and passages 15, 30, 60, 90, 144, and 200. The results showed that the variations increased with the viral passage. The nucleotides sequences of non-structural protein (NSP)2, NSP4-7, NSP10, NSP12 and NSP13 genes did not change during the Vero cell adaptation process. After comparison of the variation characteristic of classical, variant virulent/attenuated strains, it was found that attenuation of PEDV virus was associated with 9-26 amino acid (aa) changes in open reading frames (ORF) 1a/b and S protein, early termination in ORF3, 1–3 aa changes in E, M and N protein and some nucleotide sequences’ synonymous mutations. The aa deletion at about 144 aa of S protein could be the attenuation marker for the PEDV. The pig study showed that the early termination in ORF3 was more important for virus cell adaptation than virus attenuation. Full article

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

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17 pages, 772 KiB

Open AccessReview

Identifying Recent HIV Infections: From Serological Assays to Genomics

by Sikhulile Moyo^1,2,*, Eduan Wilkinson³, Vladimir Novitsky^2,4, Alain Vandormael³, Simani Gaseitsiwe^2,4, Max Essex^2,4, Susan Engelbrecht^1,5

and Tulio De Oliveira^3,6,7,*

¹ Division of Medical Virology, Stellenbosch University, Tygerberg 7505, South Africa

² Botswana-Harvard AIDS Institute Partnership, Private Bag BO320, Gaborone, Botswana

³ Africa Centre for Health and Population Studies, Doris Duke Medical Research Centre, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban 4041, South Africa

⁴ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA

⁵ National Health Laboratory Services (NHLS), Tygerberg Coastal, Johannesburg 2001, South Africa

⁶ Research Department of Infection, University College London, London WC1E 6BT, UK

⁷ College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa

Viruses 2015, 7(10), 5508-5524; https://doi.org/10.3390/v7102887 - 23 Oct 2015

Cited by 28 | Viewed by 8641

Abstract

In this paper, we review serological and molecular based methods to identify HIV infection recency. The accurate identification of recent HIV infection continues to be an important research area and has implications for HIV prevention and treatment interventions. Longitudinal cohorts that follow HIV [...] Read more.

In this paper, we review serological and molecular based methods to identify HIV infection recency. The accurate identification of recent HIV infection continues to be an important research area and has implications for HIV prevention and treatment interventions. Longitudinal cohorts that follow HIV negative individuals over time are the current gold standard approach, but they are logistically challenging, time consuming and an expensive enterprise. Methods that utilize cross-sectional testing and biomarker information have become an affordable alternative to the longitudinal approach. These methods use well-characterized biological makers to differentiate between recent and established HIV infections. However, recent results have identified a number of limitations in serological based assays that are sensitive to the variability in immune responses modulated by HIV subtypes, viral load and antiretroviral therapy. Molecular methods that explore the dynamics between the timing of infection and viral evolution are now emerging as a promising approach. The combination of serological and molecular methods may provide a good solution to identify recent HIV infection in cross-sectional data. As part of this review, we present the advantages and limitations of serological and molecular based methods and their potential complementary role for the identification of HIV infection recency. Full article

(This article belongs to the Special Issue Bioinformatics and Computational Biology of Viruses)

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19 pages, 3974 KiB

Open AccessReview

The Role of Cytokines and Chemokines in Filovirus Infection

by Sandra L. Bixler^* and Arthur J. Goff

United States Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Frederick, MD 21702, USA

Viruses 2015, 7(10), 5489-5507; https://doi.org/10.3390/v7102892 - 23 Oct 2015

Cited by 56 | Viewed by 14377

Abstract

Ebola- and marburgviruses are highly pathogenic filoviruses and causative agents of viral hemorrhagic fever. Filovirus disease is characterized by a dysregulated immune response, severe organ damage, and coagulation abnormalities. This includes modulation of cytokines, signaling mediators that regulate various components of the immune [...] Read more.

Ebola- and marburgviruses are highly pathogenic filoviruses and causative agents of viral hemorrhagic fever. Filovirus disease is characterized by a dysregulated immune response, severe organ damage, and coagulation abnormalities. This includes modulation of cytokines, signaling mediators that regulate various components of the immune system as well as other biological processes. Here we examine the role of cytokines in filovirus infection, with an emphasis on understanding how these molecules affect development of the antiviral immune response and influence pathology. These proteins may present targets for immune modulation by therapeutic agents and vaccines in an effort to boost the natural immune response to infection and/or reduce immunopathology. Full article

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

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13 pages, 4689 KiB

Open AccessArticle

Complete Genome and Phylogeny of Puumala Hantavirus Isolates Circulating in France

by Guillaume Castel^1,2,*,†, Mathilde Couteaudier^3,†, Frank Sauvage^4,5, Jean-Baptiste Pons^4,5, Séverine Murri⁶, Angelina Plyusnina⁷, Dominique Pontier^4,5, Jean-François Cosson^1,8

, Alexander Plyusnin⁷, Philippe Marianneau^6,‡ and Noël Tordo^9,‡

¹ INRA-UMR 1062 CBGP, 755 Avenue Campus Agropolis, CS30016, 34988 Montferrier sur Lez, France

² Institut de Biologie Computationnelle, 34095 Montpellier, France

³ INRA-UR1282, Biologie Virus Aviaire, 37380 Nouzilly, France

⁴ CNRS-Université Lyon 1, Laboratoire de Biométrie et Biologie Evolutive (UMR5558), F-69622 Villeurbanne, France

⁵ LabEx ECOFECT Ecoevolutionary Dynamics of Infectious Diseases, 69622 Villeurbanne, France

⁶ ANSES-Laboratoire de Lyon, Unité Virologie, 31 Avenue Tony Garnier, 69007 Lyon, France

⁷ Department of Virology, University of Helsinki, Helsinki FI-00014, Finland

⁸ INRA-UMR Bipar, 23 Av. Général de Gaulle, 94706 Maisons-Alfort, France

⁹ Institut Pasteur, Unité des Stratégies Antivirales, WHO collaborative Centre for Viral Haemorrhagic Fevers and Arboviruses, 25 rue du Docteur Roux, 75015 Paris, France

^† These authors contributed equally to this work.

^‡ These authors contributed equally to this work.

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Viruses 2015, 7(10), 5476-5488; https://doi.org/10.3390/v7102884 - 22 Oct 2015

Cited by 23 | Viewed by 9196

Abstract

Puumala virus (PUUV) is the agent of nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) in Europe. NE incidence presents a high spatial variation throughout France, while the geographical distribution of the wild reservoir of PUUV, the bank [...] Read more.

Puumala virus (PUUV) is the agent of nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) in Europe. NE incidence presents a high spatial variation throughout France, while the geographical distribution of the wild reservoir of PUUV, the bank vole, is rather continuous. A missing piece of the puzzle is the current distribution and the genetic variation of PUUV in France, which has been overlooked until now and remains poorly understood. During a population survey, from 2008 to 2011, bank voles were trapped in eight different forests of France located in areas known to be endemic for NE or in area from where no NE case has been reported until now. Bank voles were tested for immunoglobulin (Ig)G ELISA serology and two seropositive animals for each of three different areas (Ardennes, Jura and Orleans) were then subjected to laboratory analyses in order to sequence the whole S, M and L segments of PUUV. Phylogenetic analyses revealed that French PUUV isolates globally belong to the central European (CE) lineage although isolates from Ardennes are clearly distinct from those in Jura and Orleans, suggesting a different evolutionary history and origin of PUUV introduction in France. Sequence analyses revealed specific amino acid signatures along the N protein, including in PUUV from the Orleans region from where NE in humans has never been reported. The relevance of these mutations in term of pathophysiology is discussed. Full article

(This article belongs to the Section Animal Viruses)

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33 pages, 2881 KiB

Open AccessArticle

Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants

by Peter Hraber^1,*, Bette Korber¹, Kshitij Wagh¹, Elena E. Giorgi¹, Tanmoy Bhattacharya^1,2, S. Gnanakaran¹, Alan S. Lapedes¹, Gerald H. Learn³, Edward F. Kreider³, Yingying Li³, George M. Shaw³, Beatrice H. Hahn³, David C. Montefiori⁴, S. Munir Alam⁴, Mattia Bonsignori⁴, M. Anthony Moody⁴, Hua-Xin Liao⁴, Feng Gao⁴ and Barton F. Haynes⁴

¹ Los Alamos National Laboratory, Los Alamos, NM 87545, USA

² Santa Fe Institute, Santa Fe, NM 87501, USA

³ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

⁴ Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA

Viruses 2015, 7(10), 5443-5475; https://doi.org/10.3390/v7102881 - 21 Oct 2015

Cited by 26 | Viewed by 8654

Abstract

Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations [...] Read more.

Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations of mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. With well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines. Full article

(This article belongs to the Special Issue Bioinformatics and Computational Biology of Viruses)

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15 pages, 1388 KiB

Open AccessReview

Perspective of Use of Antiviral Peptides against Influenza Virus

by Sylvie Skalickova¹, Zbynek Heger^1,2, Ludmila Krejcova¹, Vladimir Pekarik¹, Karel Bastl³, Jozef Janda⁴, Frantisek Kostolansky⁵, Eva Vareckova⁵

, Ondrej Zitka^1,2, Vojtech Adam^1,2 and Rene Kizek^1,2,*

¹ Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, Brno CZ-613 00, Czech Republic

² Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, Brno CZ-616 00, Czech Republic

³ Wool and Knitting Research Institute, Brno, Sujanovo namesti 3, Brno CZ-602 00, Czech Republic

⁴ Laboratory of Tumour Biology, Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Libechov CZ-277 21, Czech Republic

⁵ Institute of Virology, Slovak Academy of Sciences, Dubravska cesta 9, 84505 Bratislava, Slovak Republic

Viruses 2015, 7(10), 5428-5442; https://doi.org/10.3390/v7102883 - 20 Oct 2015

Cited by 117 | Viewed by 14064

Abstract

The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral [...] Read more.

The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20^th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides. Full article

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

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18 pages, 1457 KiB

Open AccessReview

Diagnosis of Dengue Infection Using Conventional and Biosensor Based Techniques

by Om Parkash^* and Rafidah Hanim Shueb

Department of Medical Microbiology and Parasitology, School of Medical Science, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

Viruses 2015, 7(10), 5410-5427; https://doi.org/10.3390/v7102877 - 19 Oct 2015

Cited by 99 | Viewed by 19029

Abstract

Dengue is an arthropod-borne viral disease caused by four antigenically different serotypes of dengue virus. This disease is considered as a major public health concern around the world. Currently, there is no licensed vaccine or antiviral drug available for the prevention and treatment [...] Read more.

Dengue is an arthropod-borne viral disease caused by four antigenically different serotypes of dengue virus. This disease is considered as a major public health concern around the world. Currently, there is no licensed vaccine or antiviral drug available for the prevention and treatment of dengue disease. Moreover, clinical features of dengue are indistinguishable from other infectious diseases such as malaria, chikungunya, rickettsia and leptospira. Therefore, prompt and accurate laboratory diagnostic test is urgently required for disease confirmation and patient triage. The traditional diagnostic techniques for the dengue virus are viral detection in cell culture, serological testing, and RNA amplification using reverse transcriptase PCR. This paper discusses the conventional laboratory methods used for the diagnosis of dengue during the acute and convalescent phase and highlights the advantages and limitations of these routine laboratory tests. Subsequently, the biosensor based assays developed using various transducers for the detection of dengue are also reviewed. Full article

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22 pages, 8772 KiB

Open AccessArticle

Sequence and Structure Analysis of Distantly-Related Viruses Reveals Extensive Gene Transfer between Viruses and Hosts and among Viruses

by Silvia Caprari^1,†, Saskia Metzler^1,2,†, Thomas Lengauer¹ and Olga V. Kalinina^1,*

¹ Department for Computational Biology and Applied Algorithmics, Max Planck Institute for Informatics, Campus E1 4, 66123 Saarbrücken, Germany

² Saarbrücken Graduate School of Computer Science, University of Saarland, Campus E1 3, 66123 Saarbrücken, Germany

^† These authors contributed equally to this work.

Viruses 2015, 7(10), 5388-5409; https://doi.org/10.3390/v7102882 - 19 Oct 2015

Cited by 15 | Viewed by 9129

Abstract

The origin and evolution of viruses is a subject of ongoing debate. In this study, we provide a full account of the evolutionary relationships between proteins of significant sequence and structural similarity found in viruses that belong to different classes according to the [...] Read more.

The origin and evolution of viruses is a subject of ongoing debate. In this study, we provide a full account of the evolutionary relationships between proteins of significant sequence and structural similarity found in viruses that belong to different classes according to the Baltimore classification. We show that such proteins can be found in viruses from all Baltimore classes. For protein families that include these proteins, we observe two patterns of the taxonomic spread. In the first pattern, they can be found in a large number of viruses from all implicated Baltimore classes. In the other pattern, the instances of the corresponding protein in species from each Baltimore class are restricted to a few compact clades. Proteins with the first pattern of distribution are products of so-called viral hallmark genes reported previously. Additionally, this pattern is displayed by the envelope glycoproteins from Flaviviridae and Bunyaviridae and helicases of superfamilies 1 and 2 that have homologs in cellular organisms. The second pattern can often be explained by horizontal gene transfer from the host or between viruses, an example being Orthomyxoviridae and Coronaviridae hemagglutinin esterases. Another facet of horizontal gene transfer comprises multiple independent introduction events of genes from cellular organisms into otherwise unrelated viruses. Full article

(This article belongs to the Special Issue Bioinformatics and Computational Biology of Viruses)

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13 pages, 1097 KiB

Open AccessReview

Emerging Roles of Viroporins Encoded by DNA Viruses: Novel Targets for Antivirals?

by Jamie Royle, Samuel John Dobson, Marietta Müller and Andrew Macdonald^*

School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK

Viruses 2015, 7(10), 5375-5387; https://doi.org/10.3390/v7102880 - 16 Oct 2015

Cited by 23 | Viewed by 7763

Abstract

Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. These viroporins mediate the flow of ions and a range of solutes across cellular membranes [...] Read more.

Studies have highlighted the essential nature of a group of small, highly hydrophobic, membrane embedded, channel-forming proteins in the life cycles of a growing number of RNA viruses. These viroporins mediate the flow of ions and a range of solutes across cellular membranes and are necessary for manipulating a myriad of host processes. As such they contribute to all stages of the virus life cycle. Recent discoveries have identified proteins encoded by the small DNA tumor viruses that display a number of viroporin like properties. This review article summarizes the recent developments in our understanding of these novel viroporins; describes their roles in the virus life cycles and in pathogenesis and speculates on their potential as targets for anti-viral therapeutic intervention. Full article

(This article belongs to the Special Issue Viroporins)

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14 pages, 2585 KiB

Open AccessArticle

Respiratory Syncytial Virus Persistence in Murine Macrophages Impairs IFN-β Response but Not Synthesis

by Evelyn Rivera-Toledo, Laura Torres-González and Beatriz Gómez^*

Department of Microbiology and Parasitology, Faculty of Medicine, National Autonomous University of Mexico (UNAM), Ciudad Universitaria, D.F. Mexico C.P. 04510, Mexico

Viruses 2015, 7(10), 5361-5374; https://doi.org/10.3390/v7102879 - 16 Oct 2015

Cited by 11 | Viewed by 7256

Abstract

Type-I interferon (IFN-I) production is an early response to viral infection and pathogenic viruses have evolved multiple strategies to evade this cellular defense. Some viruses can establish and maintain persistent infections by altering the IFN-I signaling pathway. Here, we studied IFN-I synthesis and [...] Read more.

Type-I interferon (IFN-I) production is an early response to viral infection and pathogenic viruses have evolved multiple strategies to evade this cellular defense. Some viruses can establish and maintain persistent infections by altering the IFN-I signaling pathway. Here, we studied IFN-I synthesis and response in an in vitro model of persistent infection by respiratory syncytial virus (RSV) in a murine macrophage-like cell line. In this model, interferon regulatory factor 3 was constitutively active and located at nuclei of persistently infected cells, inducing expression of IFN-beta mRNA and protein. However, persistently infected macrophages did not respond in an autocrine manner to the secreted-IFN-beta or to recombinant-IFN-beta, since phosphorylated-STAT1 was not detected by western blot and transcription of the interferon-stimulated genes (ISGs) Mx1 and ISG56 was not induced. Treatment of non-infected macrophages with supernatants from persistently infected cells induced STAT1 phosphorylation and ISGs expression, mediated by the IFN-I present in the supernatants, because blocking the IFN-I receptor inhibited STAT1 phosphorylation. Results suggest that the lack of autocrine response to IFN-I by the host cell may be one mechanism for maintenance of RSV persistence. Furthermore, STAT1 phosphorylation and ISGs expression induced in non-infected cells by supernatants from persistently infected macrophages suggest that RSV persistence may trigger a proinflammatory phenotype in non-infected cells as part of the pathogenesis of RSV infection. Full article

(This article belongs to the Section Animal Viruses)

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18 pages, 3442 KiB

Open AccessArticle

A 2,5-Dihydroxybenzoic Acid–Gelatin Conjugate: The Synthesis, Antiviral Activity and Mechanism of Antiviral Action Against Two Alphaherpesviruses

by Alexander Lisov^1,*,†, Veronika Vrublevskaya^2,†, Zoy Lisova¹, Alexey Leontievsky^1,3 and Oleg Morenkov^2,3

¹ Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, Prospekt Nauki 5, Pushchino, Moscow Region 142290, Russia

² Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia

³ Pushchino State Institute of Life Sciences, ProspektNauki 3, Pushchino, Moscow Region 142290, Russia

^† These authors contributed equally to this work.

Viruses 2015, 7(10), 5343-5360; https://doi.org/10.3390/v7102878 - 15 Oct 2015

Cited by 21 | Viewed by 7718

Abstract

Various natural and synthetic polyanionic polymers with different chemical structures are known to exhibit potent antiviral activity in vitro toward a variety of enveloped viruses and may be considered as promising therapeutic agents. A water-soluble conjugate of 2,5-dihydroxybezoic acid (2,5-DHBA) with gelatin was [...] Read more.

Various natural and synthetic polyanionic polymers with different chemical structures are known to exhibit potent antiviral activity in vitro toward a variety of enveloped viruses and may be considered as promising therapeutic agents. A water-soluble conjugate of 2,5-dihydroxybezoic acid (2,5-DHBA) with gelatin was synthesized by laccase-catalyzed oxidation of 2,5-DHBA in the presence of gelatin, and its antiviral activity against pseudorabies virus (PRV) and bovine herpesvirus type 1 (BoHV-1), two members of the Alphaherpesvirinae subfamily, was studied. The conjugate produced no direct cytotoxic effect on cells, and did not inhibit cell growth at concentrations up to 1000 µg/mL. It exhibited potent antiviral activity against PRV (IC50, 1.5–15 µg/mL for different virus strains) and BoHV-1 (IC₅₀, 0.5–0.7 µg/mL). When present during virus adsorption, the conjugate strongly inhibited the attachment of PRV and BoHV-1 to cells. The 2,5-DHBA–gelatin conjugate had no direct virucidal effect on the viruses and did not influence their penetration into cells, cell-to-cell spread, production of infectious virus particles in cells, and expression of PRV glycoproteins E and B. The results indicated that the 2,5-DHBA–gelatin conjugate strongly inhibits the adsorption of alphaherpesviruses to cells and can be a promising synthetic polymer for the development of antiviral formulations against alphaherpesvirus infections. Full article

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

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15 pages, 746 KiB

Open AccessReview

HCV Drug Resistance Challenges in Japan: The Role of Pre-Existing Variants and Emerging Resistant Strains in Direct Acting Antiviral Therapy

by Kazuaki Chayama^1,2,3,* and C. Nelson Hayes^1,3

¹ Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan

² Laboratory for Digestive Diseases, Center for Genomic Medicine, Institute of Physical and Chemical Research (RIKEN), Hiroshima 734-8551, Japan

³ Liver Research Project Center, Hiroshima University, Hiroshima 734-8551, Japan

Viruses 2015, 7(10), 5328-5342; https://doi.org/10.3390/v7102876 - 13 Oct 2015

Cited by 33 | Viewed by 10582

Abstract

Sustained virological response (SVR) rates have increased dramatically following the approval of direct acting antiviral (DAA) therapies. While individual DAAs have a low barrier to resistance, most patients can be successfully treated using DAA combination therapy. However, DAAs are vulnerable to drug resistance, [...] Read more.

Sustained virological response (SVR) rates have increased dramatically following the approval of direct acting antiviral (DAA) therapies. While individual DAAs have a low barrier to resistance, most patients can be successfully treated using DAA combination therapy. However, DAAs are vulnerable to drug resistance, and resistance-associated variants (RAVs) may occur naturally prior to DAA therapy or may emerge following drug exposure. While most RAVs are quickly lost in the absence of DAAs, compensatory mutations may reinforce fitness. However, the presence of RAVs does not necessarily preclude successful treatment. Although developments in hepatitis C virus (HCV) therapy in Asia have largely paralleled those in the United States, Japan’s July 2014 approval of asunaprevir plus daclatasvir combination therapy as the first all-oral interferon-free therapy was not repeated in the United States. Instead, two different combination therapies were approved: sofosbuvir/ledipasvir and paritaprevir/ritonavir/ombitasvir/dasabuvir. This divergence in treatment approaches may lead to differences in resistance challenges faced by Japan and the US. However, the recent approval of sofosbuvir plus ledipasvir in Japan and the recent submissions of petitions for approval of paritaprevir/ritonavir plus ombitasvir suggest a trend towards a new consensus on emerging DAA regimens. Full article

(This article belongs to the Special Issue HCV Drug Resistance)

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9 pages, 3703 KiB

Open AccessCommunication

Multi-Modal Imaging with a Toolbox of Influenza AReporter Viruses

by Vy Tran^1,2, Daniel S. Poole¹, Justin J. Jeffery³, Timothy P. Sheahan⁴, Donald Creech⁴, Aleksey Yevtodiyenko⁵, Andrew J. Peat⁴, Kevin P. Francis⁵, Shihyun You⁴ and Andrew Mehle^1,*

¹ Medical Microbiology and Immunology, University of Wisconsin Madison, Madison, WI 53706, USA

² Microbiology Doctoral Training Program, University of Wisconsin Madison, Madison, WI 53706, USA

³ Carbone Cancer Center, University of Wisconsin Madison, Madison, WI 53706, USA

⁴ GlaxoSmithKline, Antiviral Discovery Performance Unit, 5 Moore Drive, Research Triangle Park, NC 27709, USA

⁵ PerkinElmer, 68 Elm Street, Hopkinton, MA 01748, USA

Viruses 2015, 7(10), 5319-5327; https://doi.org/10.3390/v7102873 - 13 Oct 2015

Cited by 37 | Viewed by 7897

Abstract

Reporter viruses are useful probes for studying multiple stages of the viral life cycle. Here we describe an expanded toolbox of fluorescent and bioluminescent influenza A reporter viruses. The enhanced utility of these tools enabled kinetic studies of viral attachment, infection, and co-infection. [...] Read more.

Reporter viruses are useful probes for studying multiple stages of the viral life cycle. Here we describe an expanded toolbox of fluorescent and bioluminescent influenza A reporter viruses. The enhanced utility of these tools enabled kinetic studies of viral attachment, infection, and co-infection. Multi-modal bioluminescence and positron emission tomography–computed tomography (PET/CT) imaging of infected animals revealed that antiviral treatment reduced viral load, dissemination, and inflammation. These new technologies and applications will dramatically accelerate in vitro and in vivo influenza virus studies. Full article

(This article belongs to the Section Animal Viruses)

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14 pages, 2992 KiB

Open AccessReview

The Role of Electron Microscopy in Studying the Continuum of Changes in Membranous Structures during Poliovirus Infection

by Evan D. Rossignol, Jie E. Yang and Esther Bullitt^*

Department of Physiology & Biophysics, Boston University School of Medicine, 700 Albany Street, W302, Boston, MA 02118-2526, USA

Viruses 2015, 7(10), 5305-5318; https://doi.org/10.3390/v7102874 - 12 Oct 2015

Cited by 7 | Viewed by 7648

Abstract

Replication of the poliovirus genome is localized to cytoplasmic replication factories that are fashioned out of a mixture of viral proteins, scavenged cellular components, and new components that are synthesized within the cell due to viral manipulation/up-regulation of protein and phospholipid synthesis. These [...] Read more.

Replication of the poliovirus genome is localized to cytoplasmic replication factories that are fashioned out of a mixture of viral proteins, scavenged cellular components, and new components that are synthesized within the cell due to viral manipulation/up-regulation of protein and phospholipid synthesis. These membranous replication factories are quite complex, and include markers from multiple cytoplasmic cellular organelles. This review focuses on the role of electron microscopy in advancing our understanding of poliovirus RNA replication factories. Structural data from the literature provide the basis for interpreting a wide range of biochemical studies that have been published on virus-induced lipid biosynthesis. In combination, structural and biochemical experiments elucidate the dramatic membrane remodeling that is a hallmark of poliovirus infection. Temporal and spatial membrane modifications throughout the infection cycle are discussed. Early electron microscopy studies of morphological changes following viral infection are re-considered in light of more recent data on viral manipulation of lipid and protein biosynthesis. These data suggest the existence of distinct subcellular vesicle populations, each of which serves specialized roles in poliovirus replication processes. Full article

(This article belongs to the Special Issue Viral Replication Complexes: Structures, Functions, Applications and Inhibitors)

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31 pages, 1075 KiB

Open AccessReview

Modeling Influenza Virus Infection: A Roadmap for Influenza Research

by Alessandro Boianelli¹, Van Kinh Nguyen¹, Thomas Ebensen², Kai Schulze², Esther Wilk³, Niharika Sharma⁴, Sabine Stegemann-Koniszewski⁴, Dunja Bruder^4,5, Franklin R. Toapanta⁶, Carlos A. Guzmán², Michael Meyer-Hermann^7,8 and Esteban A. Hernandez-Vargas^1,*

¹ Systems Medicine of Infectious Diseases, Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig 38124, Germany

² Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig 38124, Germany

³ Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig 38124, Germany

⁴ Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig 38124, Germany

⁵ Infection Immunology, Institute of Medical Microbiology, Infection Control and Prevention, Otto-von-Guericke-University, Magdeburg 39106, Germany

⁶ Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA

⁷ Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig 38124, Germany

⁸ Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig 38106, Germany

Viruses 2015, 7(10), 5274-5304; https://doi.org/10.3390/v7102875 - 12 Oct 2015

Cited by 119 | Viewed by 22492

Abstract

Influenza A virus (IAV) infection represents a global threat causing seasonal outbreaks and pandemics. Additionally, secondary bacterial infections, caused mainly by Streptococcus pneumoniae, are one of the main complications and responsible for the enhanced morbidity and mortality associated with IAV infections. In spite [...] Read more.

Influenza A virus (IAV) infection represents a global threat causing seasonal outbreaks and pandemics. Additionally, secondary bacterial infections, caused mainly by Streptococcus pneumoniae, are one of the main complications and responsible for the enhanced morbidity and mortality associated with IAV infections. In spite of the significant advances in our knowledge of IAV infections, holistic comprehension of the interplay between IAV and the host immune response (IR) remains largely fragmented. During the last decade, mathematical modeling has been instrumental to explain and quantify IAV dynamics. In this paper, we review not only the state of the art of mathematical models of IAV infection but also the methodologies exploited for parameter estimation. We focus on the adaptive IR control of IAV infection and the possible mechanisms that could promote a secondary bacterial coinfection. To exemplify IAV dynamics and identifiability issues, a mathematical model to explain the interactions between adaptive IR and IAV infection is considered. Furthermore, in this paper we propose a roadmap for future influenza research. The development of a mathematical modeling framework with a secondary bacterial coinfection, immunosenescence, host genetic factors and responsiveness to vaccination will be pivotal to advance IAV infection understanding and treatment optimization. Full article

(This article belongs to the Special Issue Bioinformatics and Computational Biology of Viruses)

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17 pages, 451 KiB

Open AccessReview

Phosphorylation of Single Stranded RNA Virus Proteins and Potential for Novel Therapeutic Strategies

by Forrest Keck, Pouya Ataey, Moushimi Amaya, Charles Bailey and Aarthi Narayanan^*

National Center for Biodefense and Infectious Disease, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA 20110, USA

Viruses 2015, 7(10), 5257-5273; https://doi.org/10.3390/v7102872 - 12 Oct 2015

Cited by 40 | Viewed by 10551

Abstract

Post translational modification of proteins is a critical requirement that regulates function. Among the diverse kinds of protein post translational modifications, phosphorylation plays essential roles in protein folding, protein:protein interactions, signal transduction, intracellular localization, transcription regulation, cell cycle progression, survival and apoptosis. Protein [...] Read more.

Post translational modification of proteins is a critical requirement that regulates function. Among the diverse kinds of protein post translational modifications, phosphorylation plays essential roles in protein folding, protein:protein interactions, signal transduction, intracellular localization, transcription regulation, cell cycle progression, survival and apoptosis. Protein phosphorylation is also essential for many intracellular pathogens to establish a productive infection cycle. Preservation of protein phosphorylation moieties in pathogens in a manner that mirrors the host components underscores the co-evolutionary trajectory of pathogens and hosts, and sheds light on how successful pathogens have usurped, either in part or as a whole, the host enzymatic machinery. Phosphorylation of viral proteins for many acute RNA viruses including Flaviviruses and Alphaviruses has been demonstrated to be critical for protein functionality. This review focuses on phosphorylation modifications that have been documented to occur on viral proteins with emphasis on acutely infectious, single stranded RNA viruses. The review additionally explores the possibility of repurposing Food and Drug Administration (FDA) approved inhibitors as antivirals for the treatment of acute RNA viral infections. Full article

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14 pages, 5684 KiB

Open AccessArticle

HPV16 E6 Controls the Gap Junction Protein Cx43 in Cervical Tumour Cells

by Peng Sun¹, Li Dong², Alasdair I. MacDonald², Shahrzad Akbari², Michael Edward³, Malcolm B. Hodgins³, Scott R. Johnstone⁴ and Sheila V. Graham^2,*

¹ Feinberg School of Medicine, North Western University, Chicago, IL 60611, USA

² MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Garscube Estate, Glasgow G61 1QH, Scotland, UK

³ Dermatology, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, Scotland, UK

⁴ Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TT, Scotland, UK

Viruses 2015, 7(10), 5243-5256; https://doi.org/10.3390/v7102871 - 5 Oct 2015

Cited by 22 | Viewed by 8524

Abstract

Human papillomavirus type 16 (HPV16) causes a range of cancers including cervical and head and neck cancers. HPV E6 oncoprotein binds the cell polarity regulator hDlg (human homologue of Drosophila Discs Large). Previously we showed in vitro, and now in vivo, [...] Read more.

Human papillomavirus type 16 (HPV16) causes a range of cancers including cervical and head and neck cancers. HPV E6 oncoprotein binds the cell polarity regulator hDlg (human homologue of Drosophila Discs Large). Previously we showed in vitro, and now in vivo, that hDlg also binds Connexin 43 (Cx43), a major component of gap junctions that mediate intercellular transfer of small molecules. In HPV16-positive non-tumour cervical epithelial cells (W12G) Cx43 localised to the plasma membrane, while in W12T tumour cells derived from these, it relocated with hDlg into the cytoplasm. We now provide evidence that E6 regulates this cytoplasmic pool of Cx43. E6 siRNA depletion in W12T cells resulted in restoration of Cx43 and hDlg trafficking to the cell membrane. In C33a HPV-negative cervical tumour cells expressing HPV16 or 18 E6, Cx43 was located primarily in the cytoplasm, but mutation of the 18E6 C-terminal hDlg binding motif resulted in redistribution of Cx43 to the membrane. The data indicate for the first time that increased cytoplasmic E6 levels associated with malignant progression alter Cx43 trafficking and recycling to the membrane and the E6/hDlg interaction may be involved. This suggests a novel E6-associated mechanism for changes in Cx43 trafficking in cervical tumour cells. Full article

(This article belongs to the Special Issue Tumour Viruses)

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18 pages, 3163 KiB

Open AccessArticle

Isolation and Genome Characterization of the Virulent Staphylococcus aureus Bacteriophage SA97

by Yoonjee Chang¹, Hakdong Shin¹, Ju-Hoon Lee², Chul Jong Park³, Soon-Young Paik⁴ and Sangryeol Ryu^1,*

¹ Department of Food and Animal Biotechnology, Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Korea

² Department of Food Science and Biotechnology, Kyung Hee University, Yongin 446-701, Korea

³ Department of Dermatology, College of Medicine, the Catholic University of Korea, Seoul 137-701, Korea

⁴ Department of Microbiology, College of Medicine, the Catholic University of Korea, Seoul 137-701, Korea

Viruses 2015, 7(10), 5225-5242; https://doi.org/10.3390/v7102870 - 1 Oct 2015

Cited by 61 | Viewed by 11161

Abstract

A novel bacteriophage that infects S. aureus, SA97, was isolated and characterized. The phage SA97 belongs to the Siphoviridae family, and the cell wall teichoic acid (WTA) was found to be a host receptor of the phage SA97. Genome analysis revealed that [...] Read more.

A novel bacteriophage that infects S. aureus, SA97, was isolated and characterized. The phage SA97 belongs to the Siphoviridae family, and the cell wall teichoic acid (WTA) was found to be a host receptor of the phage SA97. Genome analysis revealed that SA97 contains 40,592 bp of DNA encoding 54 predicted open reading frames (ORFs), and none of these genes were related to virulence or drug resistance. Although a few genes associated with lysogen formation were detected in the phage SA97 genome, the phage SA97 produced neither lysogen nor transductant in S. aureus. These results suggest that the phage SA97 may be a promising candidate for controlling S. aureus. Full article

(This article belongs to the Section Bacterial Viruses)

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19 pages, 1646 KiB

Open AccessReview

Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance

by Auda A. Eltahla¹, Fabio Luciani¹, Peter A. White²

, Andrew R. Lloyd¹ and Rowena A. Bull^1,*

¹ Systems Medicine, Inflammation and Infection Research Centre, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney 2052, Australia

² School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney 2052, Australia

Viruses 2015, 7(10), 5206-5224; https://doi.org/10.3390/v7102868 - 29 Sep 2015

Cited by 101 | Viewed by 14006

Abstract

The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The [...] Read more.

The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development, and direct-acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens. Full article

(This article belongs to the Special Issue HCV Drug Resistance)

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15 pages, 296 KiB

Open AccessArticle

Differentially-Expressed Pseudogenes in HIV-1 Infection

by Aditi Gupta^1,2,*, C. Titus Brown^1,2,3,†, Yong-Hui Zheng^1,2

and Christoph Adami^1,2,4

¹ Department of Microbiology and Molecular Genetics, Michigan State University, 567 Wilson Road, East Lansing, MI 48824, USA

² BEACON Center for the Study of Evolution in Action, Michigan State University, 567Wilson Road, East Lansing, MI 48824, USA

³ Department of Computer Science and Engineering, Michigan State University, 428 S. Shaw Lane, East Lansing, MI 48824, USA

⁴ Department of Physics and Astronomy, Michigan State University, 567 Wilson Road, East Lansing, MI 48824, USA

^† Present address: Population Health and Reproduction, University of California Davis, Davis,CA 95616, USA.

Viruses 2015, 7(10), 5191-5205; https://doi.org/10.3390/v7102869 - 29 Sep 2015

Cited by 13 | Viewed by 10554

Abstract

Not all pseudogenes are transcriptionally silent as previously thought. Pseudogene transcripts, although not translated, contribute to the non-coding RNA pool of the cell that regulates the expression of other genes. Pseudogene transcripts can also directly compete with the parent gene transcripts for mRNA [...] Read more.

Not all pseudogenes are transcriptionally silent as previously thought. Pseudogene transcripts, although not translated, contribute to the non-coding RNA pool of the cell that regulates the expression of other genes. Pseudogene transcripts can also directly compete with the parent gene transcripts for mRNA stability and other cell factors, modulating their expression levels. Tissue-specific and cancer-specific differential expression of these “functional” pseudogenes has been reported. To ascertain potential pseudogene:gene interactions in HIV-1 infection, we analyzed transcriptomes from infected and uninfected T-cells and found that 21 pseudogenes are differentially expressed in HIV-1 infection. This is interesting because parent genes of one-third of these differentially-expressed pseudogenes are implicated in HIV-1 life cycle, and parent genes of half of these pseudogenes are involved in different viral infections. Our bioinformatics analysis identifies candidate pseudogene:gene interactions that may be of significance in HIV-1 infection. Experimental validation of these interactions would establish that retroviruses exploit this newly-discovered layer of host gene expression regulation for their own benefit. Full article

(This article belongs to the Section Animal Viruses)

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Open AccessReview

Filoviruses: One of These Things is (not) Like the Other

by Scott M. Anthony¹ and Steven B. Bradfute^2,*

¹ Immunology Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA

² University of New Mexico, Center for Global Health, Department of Internal Medicine

Viruses 2015, 7(10), 5172-5190; https://doi.org/10.3390/v7102867 - 29 Sep 2015

Cited by 23 | Viewed by 8124

Abstract

The family Filoviridae contains several of the most deadly pathogens known to date and the current Ebola virus disease (EVD) outbreak in Western Africa, due to Ebola virus (EBOV) infection, highlights the need for active and broad research into filovirus pathogenesis. However, in [...] Read more.

The family Filoviridae contains several of the most deadly pathogens known to date and the current Ebola virus disease (EVD) outbreak in Western Africa, due to Ebola virus (EBOV) infection, highlights the need for active and broad research into filovirus pathogenesis. However, in comparison, the seven other known filovirus family members are significantly understudied. Many of these, including Marburgviruses and Ebolaviruses other than EBOV, are also highly virulent and fully capable of causing widespread epidemics. This review places the focus on these non-EBOV filoviruses, including known immunological and pathological data. The available animal models, research tools and currently available therapeutics will also be discussed along with an emphasis in the large number of current gaps in knowledge of these less highlighted filoviruses. It is evident that much research is yet to be done in order to bring the non-EBOV filovirus field to the forefront of current research and, importantly, to the development of more effective vaccines and therapeutics to combat potential future outbreaks. Full article

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

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Viruses, Volume 7, Issue 10 (October 2015) – 31 articles

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