Viruses

9 pages, 1435 KiB

Open AccessArticle

Engineering RNA Virus Interference via the CRISPR/Cas13 Machinery in Arabidopsis

by Rashid Aman, Ahmed Mahas, Haroon Butt, Zahir Ali, Fatimah Aljedaani

and Magdy Mahfouz^*

Laboratory for Genome Engineering, Division of Biological Sciences, 4700 King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia

Viruses 2018, 10(12), 732; https://doi.org/10.3390/v10120732 - 19 Dec 2018

Cited by 94 | Viewed by 10034

Abstract

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are key immune mechanisms helping prokaryotic species fend off RNA and DNA viruses. CRISPR/Cas9 has broad applications in basic research and biotechnology and has been widely used across eukaryotic species for genome [...] Read more.

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are key immune mechanisms helping prokaryotic species fend off RNA and DNA viruses. CRISPR/Cas9 has broad applications in basic research and biotechnology and has been widely used across eukaryotic species for genome engineering and functional analysis of genes. The recently developed CRISPR/Cas13 systems target RNA rather than DNA and thus offer new potential for transcriptome engineering and combatting RNA viruses. Here, we used CRISPR/LshCas13a to stably engineer Arabidopsis thaliana for interference against the RNA genome of Turnip mosaic virus (TuMV). Our data demonstrate that CRISPR RNAs (crRNAs) guiding Cas13a to the sequences encoding helper component proteinase silencing suppressor (HC-Pro) or GFP target 2 (GFP-T2) provide better interference compared to crRNAs targeting other regions of the TuMV RNA genome. This work demonstrates the exciting potential of CRISPR/Cas13 to be used as an antiviral strategy to obstruct RNA viruses, and encourages the search for more robust and effective Cas13 variants or CRISPR systems that can target RNA. Full article

(This article belongs to the Special Issue Applications of CRISPR Technology in Virology 2018)

▼ Show Figures

Figure 1

28 pages, 5702 KiB

Open AccessArticle

Global Interactomics Connect Nuclear Mitotic Apparatus Protein NUMA1 to Influenza Virus Maturation

by Md Niaz Rahim^1,2

, Ludger Klewes^3,4, Ali Zahedi-Amiri^1,2, Sabine Mai^3,4

and Kevin M. Coombs^1,2,5,*

¹ Department of Medical Microbiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J6, Canada

² Manitoba Centre for Proteomics & Systems Biology, Room 799, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada

³ Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J6, Canada

⁴ Genomic Centre for Cancer Research and Diagnosis, Research Institute in Oncology and Hematology, ON6026-675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada

⁵ Children’s Hospital Research Institute of Manitoba, Room 513, John Buhler Research Centre, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada

Viruses 2018, 10(12), 731; https://doi.org/10.3390/v10120731 - 19 Dec 2018

Cited by 6 | Viewed by 6846

Abstract

Influenza A virus (IAV) infections remain a major human health threat. IAV has enormous genetic plasticity and can rapidly escape virus-targeted anti-viral strategies. Thus, there is increasing interest to identify host proteins and processes the virus requires for replication and maturation. The IAV [...] Read more.

Influenza A virus (IAV) infections remain a major human health threat. IAV has enormous genetic plasticity and can rapidly escape virus-targeted anti-viral strategies. Thus, there is increasing interest to identify host proteins and processes the virus requires for replication and maturation. The IAV non-structural protein 1 (NS1) is a critical multifunctional protein that is expressed to high levels in infected cells. Host proteins that interact with NS1 may serve as ideal targets for attenuating IAV replication. We previously developed and characterized broadly cross-reactive anti-NS1 monoclonal antibodies. For the current study, we used these mAbs to co-immunoprecipitate native IAV NS1 and interacting host proteins; 183 proteins were consistently identified in this NS1 interactome study, 124 of which have not been previously reported. RNAi screens identified 11 NS1-interacting host factors as vital for IAV replication. Knocking down one of these, nuclear mitotic apparatus protein 1 (NUMA1), dramatically reduced IAV replication. IAV genomic transcription and translation were not inhibited but transport of viral structural proteins to the cell membrane was hindered during maturation steps in NUMA1 knockdown (KD) cells. Full article

(This article belongs to the Special Issue CSV2018: The 2nd symposium of the Canadian Society for Virology (CSV))

▼ Show Figures

Figure 1

19 pages, 3778 KiB

Open AccessArticle

Simultaneous Detection of Beta and Gamma Human Herpesviruses by Multiplex qPCR Reveals Simple Infection and Coinfection Episodes Increasing Risk for Graft Rejection in Solid Organ Transplantation

by Yessica Sánchez-Ponce^1,2, Gustavo Varela-Fascinetto³, José Carlos Romo-Vázquez⁴, Briceida López-Martínez⁵, José Luis Sánchez-Huerta⁶

, Israel Parra-Ortega⁶, Ezequiel M. Fuentes-Pananá^1,†

and Abigail Morales-Sánchez^1,*,†

¹ Research Unit in Virology and Cancer, Children’s Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico

² Postgraduate Program in Biological Science, National Autonomous University of Mexico, 04510 Mexico City, Mexico

³ Department of Transplantation, Children’s Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico

⁴ Department of Nephrology, Children’s Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico

⁵ Subdirection of Diagnostic Auxiliary Services, Children’s Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico

⁶ Department of Clinical Laboratory, Children’s Hospital of Mexico Federico Gómez, 06720 Mexico City, Mexico

^† These authors contributed equally to this work.

Viruses 2018, 10(12), 730; https://doi.org/10.3390/v10120730 - 19 Dec 2018

Cited by 26 | Viewed by 6025

Abstract

Herpesviruses are common components of the human microbiome that become clinically relevant when a competent immunosurveillance is compromised, such as in transplantation. Members of the beta and gamma subfamilies are associated with a wide diversity of pathologies, including end-organ disease and cancer. In [...] Read more.

Herpesviruses are common components of the human microbiome that become clinically relevant when a competent immunosurveillance is compromised, such as in transplantation. Members of the beta and gamma subfamilies are associated with a wide diversity of pathologies, including end-organ disease and cancer. In this study, we developed a multiplex qPCR technique with high specificity, sensitivity, efficiency and predictability that allowed the simultaneous detection and quantification of beta and gamma human herpesviruses. The technique was tested in a cohort of 34 kidney- or liver-transplanted pediatric patients followed up for up to 12 months post-transplant. Viral load was determined in 495 leukocyte-plasma paired samples collected bi-weekly or monthly. Human herpesvirus (HHV) 7 was the herpesvirus most frequently found in positive samples (39%), followed by Epstein-Barr virus (EBV) (20%). Also, EBV and HHV7 were present in the majority of coinfection episodes (62%). The share of positive samples exclusively detected either in leukocytes or plasma was 85%, suggesting that these herpesviruses tended to take a latent or lytic path in an exclusive manner. Infection by human cytomegalovirus (HCMV) and HHV6, as well as coinfection by EBV/HHV7 and EBV/HHV6/HHV7, were associated with graft rejection (RR = 40.33 (p = 0.0013), 5.60 (p = 0.03), 5.60 (p = 0.03) and 17.64 (p = 0.0003), respectively). The routine monitoring of beta and gamma herpesviruses should be mandatory in transplant centers to implement preventive strategies. Full article

(This article belongs to the Section Animal Viruses)

▼ Show Figures

Figure 1

35 pages, 3672 KiB

Open AccessReview

Cervical Cancer Screening Programs in Europe: The Transition Towards HPV Vaccination and Population-Based HPV Testing

by Andreas C. Chrysostomou¹, Dora C. Stylianou¹, Anastasia Constantinidou² and Leondios G. Kostrikis^1,*

¹ Department of Biological Sciences, University of Cyprus, 1 University Avenue, Aglantzia 2109, Nicosia, Cyprus

² Medical School, University of Cyprus, Shakolas Educational Center for Clinical Medicine, Palaios dromos Lefkosias Lemesou No.215/6 2029 Aglantzia, Nicosia, Cyprus

Viruses 2018, 10(12), 729; https://doi.org/10.3390/v10120729 - 19 Dec 2018

Cited by 197 | Viewed by 16323

Abstract

Cervical cancer is the fourth most frequently occurring cancer in women around the world and can affect them during their reproductive years. Since the development of the Papanicolaou (Pap) test, screening has been essential in identifying cervical cancer at a treatable stage. With [...] Read more.

Cervical cancer is the fourth most frequently occurring cancer in women around the world and can affect them during their reproductive years. Since the development of the Papanicolaou (Pap) test, screening has been essential in identifying cervical cancer at a treatable stage. With the identification of the human papillomavirus (HPV) as the causative agent of essentially all cervical cancer cases, HPV molecular screening tests and HPV vaccines for primary prevention against the virus have been developed. Accordingly, comparative studies were designed to assess the performance of cervical cancer screening methods in order to devise the best screening strategy possible. This review critically assesses the current cervical cancer screening methods as well as the implementation of HPV vaccination in Europe. The most recent European Guidelines and recommendations for organized population-based programs with HPV testing as the primary screening method are also presented. Lastly, the current landscape of cervical cancer screening programs is assessed for both European Union member states and some associated countries, in regard to the transition towards population-based screening programs with primary HPV testing. Full article

(This article belongs to the Section Animal Viruses)

▼ Show Figures

Figure 1

17 pages, 2031 KiB

Open AccessArticle

Contemporary Zika Virus Isolates Induce More dsRNA and Produce More Negative-Strand Intermediate in Human Astrocytoma Cells

by Trisha R. Barnard¹, Maaran M. Rajah¹ and Selena M. Sagan^1,2,*

¹ Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada

² Department of Biochemistry, McGill University, Montreal, QC H3A 2B4, Canada

Viruses 2018, 10(12), 728; https://doi.org/10.3390/v10120728 - 19 Dec 2018

Cited by 18 | Viewed by 5588

Abstract

The recent emergence and rapid geographic expansion of Zika virus (ZIKV) poses a significant challenge for public health. Although historically causing only mild febrile illness, recent ZIKV outbreaks have been associated with more severe neurological complications, such as Guillain-Barré syndrome and fetal microcephaly. [...] Read more.

The recent emergence and rapid geographic expansion of Zika virus (ZIKV) poses a significant challenge for public health. Although historically causing only mild febrile illness, recent ZIKV outbreaks have been associated with more severe neurological complications, such as Guillain-Barré syndrome and fetal microcephaly. Here we demonstrate that two contemporary (2015) ZIKV isolates from Puerto Rico and Brazil may have increased replicative fitness in human astrocytoma cells. Over a single infectious cycle, the Brazilian isolate replicates to higher titers and induces more severe cytopathic effects in human astrocytoma cells than the historical African reference strain or an early Asian lineage isolate. In addition, both contemporary isolates induce significantly more double-stranded RNA in infected astrocytoma cells, despite similar numbers of infected cells across isolates. Moreover, when we quantified positive- and negative-strand viral RNA, we found that the Asian lineage isolates displayed substantially more negative-strand replicative intermediates than the African lineage isolate in human astrocytoma cells. However, over multiple rounds of infection, the contemporary ZIKV isolates appear to be impaired in cell spread, infecting a lower proportion of cells at a low MOI despite replicating to similar or higher titers. Taken together, our data suggests that contemporary ZIKV isolates may have evolved mechanisms that allow them to replicate with increased efficiency in certain cell types, thereby highlighting the importance of cell-intrinsic factors in studies of viral replicative fitness. Full article

(This article belongs to the Special Issue New Advances on Zika Virus Research)

▼ Show Figures

Figure 1

11 pages, 2570 KiB

Open AccessArticle

SARS-Like Coronavirus WIV1-CoV Does Not Replicate in Egyptian Fruit Bats (Rousettus aegyptiacus)

by Neeltje Van Doremalen¹, Alexandra Schäfer², Vineet D. Menachery², Michael Letko¹, Trenton Bushmaker¹, Robert J. Fischer¹, Dania M. Figueroa¹, Patrick W. Hanley³, Greg Saturday³, Ralph S. Baric² and Vincent J. Munster^1,*

¹ Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA

² Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

³ Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA

Viruses 2018, 10(12), 727; https://doi.org/10.3390/v10120727 - 19 Dec 2018

Cited by 19 | Viewed by 13195

Abstract

Severe acute respiratory syndrome (SARS)-like WIV1-coronavirus (CoV) was first isolated from Rhinolophus sinicus bats and can use the human angiotensin converting enzyme 2 (ACE2) receptor. In the current study, we investigate the ability of WIV1-CoV to infect Rousettus aegyptiacus bats. No clinical signs [...] Read more.

Severe acute respiratory syndrome (SARS)-like WIV1-coronavirus (CoV) was first isolated from Rhinolophus sinicus bats and can use the human angiotensin converting enzyme 2 (ACE2) receptor. In the current study, we investigate the ability of WIV1-CoV to infect Rousettus aegyptiacus bats. No clinical signs were observed throughout the experiment. Furthermore, only four oropharyngeal swabs and two respiratory tissues, isolated on day 3 post inoculation, were found positive for viral RNA. Two out of twelve bats showed a modest increase in coronavirus specific antibodies post challenge. In conclusion, WIV1-CoV was unable to cause a robust infection in Rousettus aegyptiacus bats. Full article

(This article belongs to the Section Animal Viruses)

▼ Show Figures

Figure 1

21 pages, 3480 KiB

Open AccessArticle

The Amino-Terminal Region of Hepatitis E Virus ORF1 Containing a Methyltransferase (Met) and a Papain-Like Cysteine Protease (PCP) Domain Counteracts Type I Interferon Response

by Eugénie Bagdassarian^1,2,3,†, Virginie Doceul^1,2,3,*,†

, Marie Pellerin^1,2,3, Antonin Demange^1,2,3,‡, Léa Meyer^1,2,3

, Nolwenn Jouvenet⁴

and Nicole Pavio^1,2,3

¹ Anses, UMR 1161 Virologie, Laboratoire de Santé Animale, 94700 Maisons-Alfort, France

² INRA, UMR 1161 Virologie, 94700 Maisons-Alfort, France

³ École Nationale Vétérinaire d’Alfort, UMR 1161 Virologie, 94700 Maisons-Alfort, France

⁴ CNRS-UMR3569, Unité de Génomique Virale et Vaccination, Institut Pasteur, 75015 Paris, France

^† These authors contributed equally to this work.

^‡ Current address: UMR CNRS 5290, IRD 224, Université de Montpellier, 34394 Montpellier, France.

Viruses 2018, 10(12), 726; https://doi.org/10.3390/v10120726 - 18 Dec 2018

Cited by 17 | Viewed by 5203

Abstract

Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide. In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 [...] Read more.

Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide. In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 and HEV-4), chronic cases of hepatitis and severe neurological disorders are reported. Hence, it is important to characterize the interactions between HEV and its host. Here, we investigated the ability of the nonstructural polyprotein encoded by the first open reading frame (ORF1) of HEV to modulate the host early antiviral response and, in particular, the type I interferon (IFN-I) system. We found that the amino-terminal region of HEV-3 ORF1 (MetYPCP), containing a putative methyltransferase (Met) and a papain-like cysteine protease (PCP) functional domain, inhibited IFN-stimulated response element (ISRE) promoter activation and the expression of several IFN-stimulated genes (ISGs) in response to IFN-I. We showed that the MetYPCP domain interfered with the Janus kinase (JAK)/signal transducer and activator of the transcription protein (STAT) signalling pathway by inhibiting STAT1 nuclear translocation and phosphorylation after IFN-I treatment. In contrast, MetYPCP had no effect on STAT2 phosphorylation and a limited impact on the activation of the JAK/STAT pathway after IFN-II stimulation. This inhibitory function seemed to be genotype-dependent, as MetYPCP from HEV-1 had no significant effect on the JAK/STAT pathway. Overall, this study provides evidence that the predicted MetYPCP domain of HEV ORF1 antagonises STAT1 activation to modulate the IFN response. Full article

(This article belongs to the Special Issue Emerging Viruses)

▼ Show Figures

Figure 1

4 pages, 179 KiB

Open AccessEditorial

One Health (r)Evolution: Learning from the Past to Build a New Future

by Ilaria Capua^1,* and Giovanni Cattoli²

¹ One Health Center of Excellence for Research and Training, University of Florida, Gainesville, FL 32611, USA

² Animal Production and Health Laboratory, Joint FAO/IAEA Division of Nuclear Technique in Food and Agriculture IAEA, Vienna International Centre, 1400 Vienna, Austria

Viruses 2018, 10(12), 725; https://doi.org/10.3390/v10120725 - 18 Dec 2018

Cited by 21 | Viewed by 6244

Abstract

The One Health concept recognizes that the health of human beings, animals, plants and the environment is interconnected and interdependent. This idea has been shaped over the centuries and has gained momentum and traction as anatomy, physiology, microbiology and other disciplines have substantiated [...] Read more.

The One Health concept recognizes that the health of human beings, animals, plants and the environment is interconnected and interdependent. This idea has been shaped over the centuries and has gained momentum and traction as anatomy, physiology, microbiology and other disciplines have substantiated earlier theories. Here we recall major historical milestones which have contributed to shaping the One Health concept as it is today, and discuss the past and future drivers in view of future challenges in an evolving scenario. Full article

(This article belongs to the Special Issue Zoonotic and Vectorborne Viral Infections: Applying the One Health Vision—from Challenges to Solutions)

6 pages, 180 KiB

Open AccessOpinion

Advances in Influenza Virus Research: A Personal Perspective

by Kanta Subbarao^1,2

¹ WHO Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia

² Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia

Viruses 2018, 10(12), 724; https://doi.org/10.3390/v10120724 - 18 Dec 2018

Cited by 3 | Viewed by 4763

Abstract

Technical advances in the last decade have made it possible to investigate influenza virus infection from the cellular and subcellular level to intact animals and humans. As a result, we have gained a new understanding of the virus and disease. Full article

(This article belongs to the Special Issue What’s New with Flu?)

13 pages, 5689 KiB

Open AccessReview

Prion Strain-Specific Structure and Pathology: A View from the Perspective of Glycobiology

by Ilia V. Baskakov^1,2,*, Elizaveta Katorcha^1,2,† and Natallia Makarava^1,2

¹ Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MA 21201, USA

² Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MA 21201, USA

^† Present address: Trace-Ability Inc., 6919B Woodley Ave, Van Nuys, CA 91406, USA.

Viruses 2018, 10(12), 723; https://doi.org/10.3390/v10120723 - 18 Dec 2018

Cited by 29 | Viewed by 5410

Abstract

Prion diseases display multiple disease phenotypes characterized by diverse clinical symptoms, different brain regions affected by the disease, distinct cell tropism and diverse PrP^Sc deposition patterns. The diversity of disease phenotypes within the same host is attributed to the ability of PrP [...] Read more.

Prion diseases display multiple disease phenotypes characterized by diverse clinical symptoms, different brain regions affected by the disease, distinct cell tropism and diverse PrP^Sc deposition patterns. The diversity of disease phenotypes within the same host is attributed to the ability of PrP^C to acquire multiple, alternative, conformationally distinct, self-replicating PrP^Sc states referred to as prion strains or subtypes. Structural diversity of PrP^Sc strains has been well documented, yet the question of how different PrP^Sc structures elicit multiple disease phenotypes remains poorly understood. The current article reviews emerging evidence suggesting that carbohydrates in the form of sialylated N-linked glycans, which are a constitutive part of PrP^Sc, are important players in defining strain-specific structures and disease phenotypes. This article introduces a new hypothesis, according to which individual strain-specific PrP^Sc structures govern selection of PrP^C sialoglycoforms that form strain-specific patterns of carbohydrate epitopes on PrP^Sc surface and contribute to defining the disease phenotype and outcomes. Full article

(This article belongs to the Special Issue Deciphering the Molecular Targets of Prion and Prion-Like Strains)

▼ Show Figures

Figure 1

9 pages, 1296 KiB

Open AccessMeeting Report

“FAGOMA: Spanish Network of Bacteriophages and Transducer Elements”—V Meeting Report

by Modesto Redrejo-Rodríguez¹

and Pilar García^2,*

¹ Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM) and Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), 28029 Madrid, Spain

² Instituto de Productos Lácteos de Asturias (IPLA-CSIC). Paseo Río Linares s/n, 33300 Villaviciosa, Asturias, Spain

Viruses 2018, 10(12), 722; https://doi.org/10.3390/v10120722 - 18 Dec 2018

Viewed by 4373

Abstract

The Spanish Network of Bacteriophages and Transducer Elements (FAGOMA) was created to answer the need of Spanish scientists working on phages to exchange knowledge and find synergies. Seven years and five meetings later, the network has become a fruitful forum where groups working [...] Read more.

The Spanish Network of Bacteriophages and Transducer Elements (FAGOMA) was created to answer the need of Spanish scientists working on phages to exchange knowledge and find synergies. Seven years and five meetings later, the network has become a fruitful forum where groups working on distinct aspects of phage research (structural and molecular biology, diversity, gene transfer and evolution, virus–host interactions, clinical, biotechnological and industrial applications) present their work and find new avenues for collaboration. The network has recently increased its visibility and activity by getting in touch with the French Phage Network (Phages.fr) and with different national and international scientific institutions. Here, we present a summary of the fifth meeting of the FAGOMA network, held in October 2018 in Alcalá de Henares (Madrid), in which the participants shared some of their latest results and discussed future challenges of phage research. Full article

(This article belongs to the Section Bacterial Viruses)

▼ Show Figures

Figure 1

25 pages, 6053 KiB

Open AccessReview

Development of Small-Molecule MERS-CoV Inhibitors

by Ruiying Liang^1,†, Lili Wang^2,†, Naru Zhang^3,†, Xiaoqian Deng¹, Meng Su¹, Yudan Su¹, Lanfang Hu¹, Chen He¹, Tianlei Ying^4,*, Shibo Jiang^4,* and Fei Yu^1,*

¹ College of Life and Science, Hebei Agricultural University, Baoding 071001, China

² Research Center of Chinese Jujube, Hebei Agricultural University, Baoding 071001, China

³ Department of Clinical Medicine, Faculty of Medicine, Zhejiang University City College, Hangzhou 310015, China

⁴ Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China

^† These authors contributed equally to this work.

Viruses 2018, 10(12), 721; https://doi.org/10.3390/v10120721 - 17 Dec 2018

Cited by 52 | Viewed by 12602

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) with potential to cause global pandemics remains a threat to the public health, security, and economy. In this review, we focus on advances in the research and development of small-molecule MERS-CoV inhibitors targeting different stages of the [...] Read more.

Middle East respiratory syndrome coronavirus (MERS-CoV) with potential to cause global pandemics remains a threat to the public health, security, and economy. In this review, we focus on advances in the research and development of small-molecule MERS-CoV inhibitors targeting different stages of the MERS-CoV life cycle, aiming to prevent or treat MERS-CoV infection. Full article

(This article belongs to the Special Issue MERS-CoV)

▼ Show Figures

Figure 1

9 pages, 5118 KiB

Open AccessArticle

A Divergent Hepatitis D-Like Agent in Birds

by Michelle Wille^1,*

, Hans J. Netter², Margaret Littlejohn²

, Lilly Yuen²

, Mang Shi³, John-Sebastian Eden³

, Marcel Klaassen⁴

, Edward C. Holmes³

and Aeron C. Hurt¹

¹ WHO Collaborating Centre for Reference and Research on Influenza, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia

² Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia

³ Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia

⁴ Centre for Integrative Ecology, Deakin University, Geelong, VIC 3220, Australia

Viruses 2018, 10(12), 720; https://doi.org/10.3390/v10120720 - 17 Dec 2018

Cited by 65 | Viewed by 7650

Abstract

Hepatitis delta virus (HDV) is currently only found in humans and is a satellite virus that depends on hepatitis B virus (HBV) envelope proteins for assembly, release, and entry. Using meta-transcriptomics, we identified the genome of a novel HDV-like agent in ducks. Sequence [...] Read more.

Hepatitis delta virus (HDV) is currently only found in humans and is a satellite virus that depends on hepatitis B virus (HBV) envelope proteins for assembly, release, and entry. Using meta-transcriptomics, we identified the genome of a novel HDV-like agent in ducks. Sequence analysis revealed secondary structures that were shared with HDV, including self-complementarity and ribozyme features. The predicted viral protein shares 32% amino acid similarity to the small delta antigen of HDV and comprises a divergent phylogenetic lineage. The discovery of an avian HDV-like agent has important implications for the understanding of the origins of HDV and sub-viral agents. Full article

(This article belongs to the Section Animal Viruses)

▼ Show Figures

Graphical abstract

10 pages, 240 KiB

Open AccessReview

Chrysanthemum Stunt Viroid Resistance in Chrysanthemum

by Tomoyuki Nabeshima^1,*

, Yosuke Matsushita²

and Munetaka Hosokawa³

¹ Experimental Farm of Agriculture, Department of Agriculture, Kyoto University, Kizugawa, Kyoto 619-0218, Japan

² Institute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization, Tsukuba, Ibaraki 305-0258, Japan

³ Laboratory of Floriculture, Department of Agriculture, Kindai University, Nara, Nara 631-0052, Japan

Viruses 2018, 10(12), 719; https://doi.org/10.3390/v10120719 - 17 Dec 2018

Cited by 5 | Viewed by 5882

Abstract

Chrysanthemum stunt viroid (CSVd) is one of the most severe threats in Chrysanthemum morifolium production. Over the last decade, several studies have reported the natural occurrence of CSVd resistance in chrysanthemum germplasms. Such CSVd-resistant germplasms are desirable for the stable production of chrysanthemum [...] Read more.

Chrysanthemum stunt viroid (CSVd) is one of the most severe threats in Chrysanthemum morifolium production. Over the last decade, several studies have reported the natural occurrence of CSVd resistance in chrysanthemum germplasms. Such CSVd-resistant germplasms are desirable for the stable production of chrysanthemum plants. Current surveys include finding new resistant chrysanthemum cultivars, breeding, and revealing resistant mechanisms. We review the progress, from discovery to current status, of CSVd-resistance studies, while introducing information on the improvement of associated inoculation and diagnostic techniques. Full article

(This article belongs to the Special Issue Viroid-2018: International Conference on Viroids and Viroid-Like RNAs)

18 pages, 2028 KiB

Open AccessArticle

CD8+ T Cells Responding to the Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Delivered by Vaccinia Virus MVA in Mice

by Svenja Veit¹, Sylvia Jany¹, Robert Fux¹, Gerd Sutter^1,2,*

and Asisa Volz^1,2

¹ Institute for Infectious Diseases and Zoonoses, LMU Munich, 80539 Munich, Germany

² German Center for Infection Research (DZIF), partner site Munich, 80539 Munich, Germany

Viruses 2018, 10(12), 718; https://doi.org/10.3390/v10120718 - 16 Dec 2018

Cited by 38 | Viewed by 6256

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV), a novel infectious agent causing severe respiratory disease and death in humans, was first described in 2012. Antibodies directed against the MERS-CoV spike (S) protein are thought to play a major role in controlling MERS-CoV infection and [...] Read more.

Middle East respiratory syndrome coronavirus (MERS-CoV), a novel infectious agent causing severe respiratory disease and death in humans, was first described in 2012. Antibodies directed against the MERS-CoV spike (S) protein are thought to play a major role in controlling MERS-CoV infection and in mediating vaccine-induced protective immunity. In contrast, relatively little is known about the role of T cell responses and the antigenic targets of MERS-CoV that are recognized by CD8+ T cells. In this study, the highly conserved MERS-CoV nucleocapsid (N) protein served as a target immunogen to elicit MERS-CoV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for generating MVA-MERS-N expressing recombinant N protein. Overlapping peptides spanning the whole MERS-CoV N polypeptide were used to identify major histocompatibility complex class I/II-restricted T cell responses in BALB/c mice immunized with MVA-MERS-N. We have identified a H2-d restricted decamer peptide epitope in the MERS-N protein with CD8+ T cell antigenicity. The identification of this epitope, and the availability of the MVA-MERS-N candidate vaccine, will help to evaluate MERS-N-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of MERS-CoV infection. Full article

(This article belongs to the Special Issue MERS-CoV)

▼ Show Figures

Figure 1

18 pages, 6012 KiB

Open AccessArticle

Strawberry Vein Banding Virus P6 Protein Is a Translation Trans-Activator and Its Activity Can be Suppressed by FveIF3g

by Shuai Li^1,†, Yahui Hu^1,†, Lei Jiang¹, Penghuan Rui¹, Qingqing Zhao¹, Jiying Feng¹, Dengpan Zuo¹, Xueping Zhou² and Tong Jiang^1,*

¹ School of Plant Protection, Anhui Agricultural University, Hefei 230036, China

² State Key Laboratory for Plant Disease and Insect Pest, Institute of Plant protection, China Academy of Agricultural Sciences, Beijing 100193, China

^† These authors contributed equally to this paper.

Viruses 2018, 10(12), 717; https://doi.org/10.3390/v10120717 - 15 Dec 2018

Cited by 9 | Viewed by 4292

Abstract

The strawberry vein banding virus (SVBV) open reading frame (ORF) VI encodes a P6 protein known as the RNA silencing suppressor. This protein is known to form inclusion like granules of various sizes and accumulate in both the nuclei and the cytoplasm of [...] Read more.

The strawberry vein banding virus (SVBV) open reading frame (ORF) VI encodes a P6 protein known as the RNA silencing suppressor. This protein is known to form inclusion like granules of various sizes and accumulate in both the nuclei and the cytoplasm of SVBV-infected plant cells. In this study, we have determined that the P6 protein is the only trans-activator (TAV) encoded by SVBV, and can efficiently trans-activate the translation of downstream gfp mRNA in a bicistron derived from the SVBV. Furthermore, the P6 protein can trans-activate the expression of different bicistrons expressed by different caulimovirus promoters. The P6 protein encoded by SVBV from an infectious clone can also trans-activate the expression of bicistron. Through protein-protein interaction assays, we determined that the P6 protein could interact with the cell translation initiation factor FveIF3g of Fragaria vesca and co-localize with it in the nuclei of Nicotiana benthamiana cells. This interaction reduced the formation of P6 granules in cells and its trans-activation activity on translation. Full article

(This article belongs to the Special Issue Fruit Tree Viruses and Viroids)

▼ Show Figures

Figure 1

12 pages, 3951 KiB

Open AccessArticle

Human Respiratory Syncytial Virus NS 1 Targets TRIM25 to Suppress RIG-I Ubiquitination and Subsequent RIG-I-Mediated Antiviral Signaling

by Junsu Ban^1,†, Na-Rae Lee^1,†, Noh-Jin Lee¹, Jong Kil Lee¹, Fu-Shi Quan^2,* and Kyung-Soo Inn^1,*

¹ Department of Fundamental Pharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Korea

² Department of Medical Zoology, School of Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Korea

^† These authors equally contributed to this study.

Viruses 2018, 10(12), 716; https://doi.org/10.3390/v10120716 - 14 Dec 2018

Cited by 63 | Viewed by 6076

Abstract

Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease. Retinoic acid-inducible gene-I (RIG-I) serves as an innate immune sensor and triggers antiviral responses upon recognizing viral infections including RSV. Since tripartite motif-containing protein 25 (TRIM25)-mediated K63-polyubiquitination is crucial for RIG-I activation, [...] Read more.

Respiratory syncytial virus (RSV) causes severe acute lower respiratory tract disease. Retinoic acid-inducible gene-I (RIG-I) serves as an innate immune sensor and triggers antiviral responses upon recognizing viral infections including RSV. Since tripartite motif-containing protein 25 (TRIM25)-mediated K63-polyubiquitination is crucial for RIG-I activation, several viruses target initial RIG-I activation through ubiquitination. RSV NS1 and NS2 have been shown to interfere with RIG-I-mediated antiviral signaling. In this study, we explored the possibility that NS1 suppresses RIG-I-mediated antiviral signaling by targeting TRIM25. Ubiquitination of ectopically expressed RIG-I-2Cards domain was decreased by RSV infection, indicating that RSV possesses ability to inhibit TRIM25-mediated RIG-I ubiquitination. Similarly, ectopic expression of NS1 sufficiently suppressed TRIM25-mediated RIG-I ubiquitination. Furthermore, interaction between NS1 and TRIM25 was detected by a co-immunoprecipitation assay. Further biochemical assays showed that the SPRY domain of TRIM25, which is responsible for interaction with RIG-I, interacted sufficiently with NS1. Suppression of RIG-I ubiquitination by NS1 resulted in decreased interaction between RIG-I and its downstream molecule, MAVS. The suppressive effect of NS1 on RIG-I signaling could be abrogated by overexpression of TRIM25. Collectively, this study suggests that RSV NS1 interacts with TRIM25 and interferes with RIG-I ubiquitination to suppress type-I interferon signaling. Full article

(This article belongs to the Section Animal Viruses)

▼ Show Figures

Figure 1

22 pages, 5272 KiB

Open AccessArticle

Seasonality Drives Microbial Community Structure, Shaping both Eukaryotic and Prokaryotic Host–Viral Relationships in an Arctic Marine Ecosystem

by Ruth-Anne Sandaa^1,*, Julia E. Storesund¹, Emily Olesin¹, Maria Lund Paulsen¹

, Aud Larsen^1,2, Gunnar Bratbak¹

and Jessica Louise Ray^1,2

¹ Department of Biosciences, University of Bergen, N-5020 Bergen, Norway

² NORCE Norwegian Research Centre AS, Uni Research Environment, N-5020 Bergen, Norway

Viruses 2018, 10(12), 715; https://doi.org/10.3390/v10120715 - 14 Dec 2018

Cited by 21 | Viewed by 6281

Abstract

The Arctic marine environment experiences dramatic seasonal changes in light and nutrient availability. To investigate the influence of seasonality on Arctic marine virus communities, five research cruises to the west and north of Svalbard were conducted across one calendar year, collecting water from [...] Read more.

The Arctic marine environment experiences dramatic seasonal changes in light and nutrient availability. To investigate the influence of seasonality on Arctic marine virus communities, five research cruises to the west and north of Svalbard were conducted across one calendar year, collecting water from the surface to 1000 m in depth. We employed metabarcoding analysis of major capsid protein g23 and mcp genes in order to investigate T4-like myoviruses and large dsDNA viruses infecting prokaryotic and eukaryotic picophytoplankton, respectively. Microbial abundances were assessed using flow cytometry. Metabarcoding results demonstrated that seasonality was the key mediator shaping virus communities, whereas depth exerted a diversifying effect within seasonal virus assemblages. Viral diversity and virus-to-prokaryote ratios (VPRs) dropped sharply at the commencement of the spring bloom but increased across the season, ultimately achieving the highest levels during the winter season. These findings suggest that viral lysis may be an important process during the polar winter, when productivity is low. Furthermore, winter viral communities consisted of Operational Taxonomic Units (OTUs) distinct from those present during the spring-summer season. Our data provided a first insight into the diversity of viruses in a hitherto undescribed marine habitat characterized by extremes in light and productivity. Full article

(This article belongs to the Special Issue Viruses of Microbes V: Biodiversity and Future Applications)

▼ Show Figures

Figure 1

22 pages, 4515 KiB

Open AccessArticle

Simultaneous Detection of Different Zika Virus Lineages via Molecular Computation in a Point-of-Care Assay

by Sanchita Bhadra^1,*

, Miguel A. Saldaña², Hannah Grace Han¹, Grant L. Hughes^3,†

and Andrew D. Ellington¹

¹ Department of Molecular Biosciences, College of Natural Sciences, The University of Texas at Austin, Austin, TX 78712, USA

² Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA

³ Department of Pathology, Institute for Human Infections and Immunity, Center for Tropical Diseases, Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston, TX 77555, USA

^† Present Address: Department of Vector Biology and Department of Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.

Viruses 2018, 10(12), 714; https://doi.org/10.3390/v10120714 - 14 Dec 2018

Cited by 10 | Viewed by 6214

Abstract

We have developed a generalizable “smart molecular diagnostic” capable of accurate point-of-care (POC) detection of variable nucleic acid targets. Our isothermal assay relies on multiplex execution of four loop-mediated isothermal amplification reactions, with primers that are degenerate and redundant, thereby increasing the breadth [...] Read more.

We have developed a generalizable “smart molecular diagnostic” capable of accurate point-of-care (POC) detection of variable nucleic acid targets. Our isothermal assay relies on multiplex execution of four loop-mediated isothermal amplification reactions, with primers that are degenerate and redundant, thereby increasing the breadth of targets while reducing the probability of amplification failure. An easy-to-read visual answer is computed directly by a multi-input Boolean OR logic gate (gate output is true if either one or more gate inputs is true) signal transducer that uses degenerate strand exchange probes to assess any combination of amplicons. We demonstrate our methodology by using the same assay to detect divergent Asian and African lineages of the evolving Zika virus (ZIKV), while maintaining selectivity against non-target viruses. Direct analysis of biological specimens proved possible, with crudely macerated ZIKV-infected Aedes aegypti mosquitoes being identified with 100% specificity and sensitivity. The ease-of-use with minimal instrumentation, broad programmability, and built-in fail-safe reliability make our smart molecular diagnostic attractive for POC use. Full article

(This article belongs to the Special Issue New Advances on Zika Virus Research)

▼ Show Figures

Figure 1

15 pages, 1855 KiB

Open AccessArticle

Transcriptional and Small RNA Responses of the White Mold Fungus Sclerotinia sclerotiorum to Infection by a Virulence-Attenuating Hypovirus

by Shin-Yi Lee Marzano^1,2,*, Achal Neupane¹

and Leslie Domier^3,*

¹ Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57006, USA

² Department of Agronomy, Horticulture, and Plant Science, South Dakota State University, Brookings, SD 57006, USA

³ United States Department of Agriculture, Agricultural Research Service, Department of Crop Sciences, University of Illinois, Urbana, IL 61801, USA

Viruses 2018, 10(12), 713; https://doi.org/10.3390/v10120713 - 14 Dec 2018

Cited by 27 | Viewed by 5675

Abstract

Mycoviruses belonging to the family Hypoviridae cause persistent infection of many different host fungi. We previously determined that the white mold fungus, Sclerotinia sclerotiorum, infected with Sclerotinia sclerotiorum hypovirus 2-L (SsHV2-L) exhibits reduced virulence, delayed/reduced sclerotial formation, and enhanced production of aerial [...] Read more.

Mycoviruses belonging to the family Hypoviridae cause persistent infection of many different host fungi. We previously determined that the white mold fungus, Sclerotinia sclerotiorum, infected with Sclerotinia sclerotiorum hypovirus 2-L (SsHV2-L) exhibits reduced virulence, delayed/reduced sclerotial formation, and enhanced production of aerial mycelia. To gain better insight into the cellular basis for these changes, we characterized changes in mRNA and small RNA (sRNA) accumulation in S. sclerotiorum to infection by SsHV2-L. A total of 958 mRNAs and 835 sRNA-producing loci were altered after infection by SsHV2-L, among which >100 mRNAs were predicted to encode proteins involved in the metabolism and trafficking of carbohydrates and lipids. Both S. sclerotiorum endogenous and virus-derived sRNAs were predominantly 22 nt in length suggesting one dicer-like enzyme cleaves both. Novel classes of endogenous small RNAs were predicted, including phasiRNAs and tRNA-derived small RNAs. Moreover, S. sclerotiorum phasiRNAs, which were derived from noncoding RNAs and have the potential to regulate mRNA abundance in trans, showed differential accumulation due to virus infection. tRNA fragments did not accumulate differentially after hypovirus infection. Hence, in-depth analysis showed that infection of S. sclerotiorum by a hypovirulence-inducing hypovirus produced selective, large-scale reprogramming of mRNA and sRNA production. Full article

(This article belongs to the Special Issue Mycoviruses)

▼ Show Figures

Figure 1

16 pages, 263 KiB

Open AccessReview

Suppression of Type I Interferon Signaling by Flavivirus NS5

by Stephanie Thurmond^1,2, Boxiao Wang³, Jikui Song^3,* and Rong Hai^1,2,*

¹ Department of Microbiology and Plant Pathology, University of California, Riverside, Riverside, CA 92521, USA

² Graduate Program in Cell, Molecular and Developmental Biology, University of California, Riverside, Riverside, CA 92521, USA

³ Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA

Viruses 2018, 10(12), 712; https://doi.org/10.3390/v10120712 - 14 Dec 2018

Cited by 41 | Viewed by 5501

Abstract

Type I interferon (IFN-I) is the first line of mammalian host defense against viral infection. To counteract this, the flaviviruses, like other viruses, have encoded a variety of antagonists, and use a multi-layered molecular defense strategy to establish their infections. Among the most [...] Read more.

Type I interferon (IFN-I) is the first line of mammalian host defense against viral infection. To counteract this, the flaviviruses, like other viruses, have encoded a variety of antagonists, and use a multi-layered molecular defense strategy to establish their infections. Among the most potent antagonists is non-structural protein 5 (NS5), which has been shown for all disease-causing flaviviruses to target different steps and players of the type I IFN signaling pathway. Here, we summarize the type I IFN antagonist mechanisms used by flaviviruses with a focus on the role of NS5 in regulating one key regulator of type I IFN, signal transducer and activator of transcription 2 (STAT2). Full article

(This article belongs to the Special Issue New Advances on Zika Virus Research)

12 pages, 4012 KiB

Open AccessArticle

Parechovirus A Detection by a Comprehensive Approach in a Clinical Laboratory

by Bao-Chen Chen¹, Jenn-Tzong Chang², Tsi-Shu Huang¹, Jih-Jung Chen^3,4

, Yao-Shen Chen^5,*, Ming-Wei Jan⁶

and Tsung-Hsien Chang^6,7,*

¹ Department of Microbiology, Kaohsiung Veterans General Hospital, Kaohsiung81362, Taiwan

² Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan

³ Faculty of Pharmacy, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan

⁴ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan

⁵ Department of Infectious Diseases, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan

⁶ Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan

⁷ Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan 717, Taiwan

Viruses 2018, 10(12), 711; https://doi.org/10.3390/v10120711 - 12 Dec 2018

Cited by 4 | Viewed by 4616

Abstract

Parechovirus A (Human parechovirus, HPeV) causes symptoms ranging from severe neonatal infection to mild gastrointestinal and respiratory disease. Use of molecular approaches with RT-PCR and genotyping has improved the detection rate of HPeV. Conventional methods, such as viral culture and immunofluorescence assay, together [...] Read more.

Parechovirus A (Human parechovirus, HPeV) causes symptoms ranging from severe neonatal infection to mild gastrointestinal and respiratory disease. Use of molecular approaches with RT-PCR and genotyping has improved the detection rate of HPeV. Conventional methods, such as viral culture and immunofluorescence assay, together with molecular methods facilitate comprehensive viral diagnosis. To establish the HPeV immunofluorescence assay, an antibody against HPeV capsid protein VP0 was generated by using antigenic epitope prediction data. The specificity of the anti-HPeV VP0 antibody was demonstrated on immunofluorescence assay, showing that this antibody was specific for HPeV but not enteroviruses. A total of 74 HPeV isolates, 7 non–polio-enteroviruses and 12 HPeV negative cell culture supernatant were used for evaluating the efficiency of the anti-HPeV VP0 antibody. The sensitivity of HPeV detection by the anti-HPeV VP0 antibody was consistent with 5′untranslated region (UTR) RT-PCR analysis. This study established comprehensive methods for HPeV detection that include viral culture and observation of cytopathic effect, immunofluorescence assay, RT-PCR and genotyping. The methods were incorporated into our routine clinical practice for viral diagnosis. In conclusion, this study established a protocol for enterovirus and HPeV virus identification that combines conventional and molecular methods and would be beneficial for HPeV diagnosis. Full article

(This article belongs to the Special Issue Emerging Viruses)

▼ Show Figures

Figure 1

23 pages, 2745 KiB

Open AccessArticle

The N-Terminus of the HIV-1 p6 Gag Protein Regulates Susceptibility to Degradation by IDE

by Adrian Schmalen¹

, Julia Karius-Fischer¹, Pia Rauch¹, Christian Setz¹, Klaus Korn¹

, Petra Henklein², Torgils Fossen³ and Ulrich Schubert^1,*

¹ Institute of Virology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany

² Institute of Biochemistry, Charité—Universitätsmedizin Berlin, 10117 Berlin, Germany

³ Department of Chemistry, University of Bergen, 5020 Bergen, Norway

Viruses 2018, 10(12), 710; https://doi.org/10.3390/v10120710 - 12 Dec 2018

Cited by 4 | Viewed by 4648

Abstract

As part of the Pr55^Gag polyprotein, p6 fulfills an essential role in the late steps of the replication cycle. However, almost nothing is known about the functions of the mature HIV-1 p6 protein. Recently, we showed that p6 is a bona fide [...] Read more.

As part of the Pr55^Gag polyprotein, p6 fulfills an essential role in the late steps of the replication cycle. However, almost nothing is known about the functions of the mature HIV-1 p6 protein. Recently, we showed that p6 is a bona fide substrate of the insulin-degrading enzyme (IDE), a ubiquitously expressed zinc metalloprotease. This phenomenon appears to be specific for HIV-1, since p6 homologs of HIV-2, SIV and EIAV were IDE-insensitive. Furthermore, abrogation of the IDE-mediated degradation of p6 reduces the replication capacity of HIV-1 in an Env-dependent manner. However, it remained unclear to which extent the IDE mediated degradation is phylogenetically conserved among HIV-1. Here, we describe two HIV-1 isolates with IDE resistant p6 proteins. Sequence comparison allowed deducing one single amino acid regulating IDE sensitivity of p6. Exchanging the N-terminal leucine residue of p6 derived from the IDE sensitive isolate HIV-1_NL4-3 with proline enhances its stability, while replacing Pro-1 of p6 from the IDE insensitive isolate SG3 with leucine restores susceptibility towards IDE. Phylogenetic analyses of this natural polymorphism revealed that the N-terminal leucine is characteristic for p6 derived from HIV-1 group M except for subtype A, which predominantly expresses p6 with an N-terminal proline. Consequently, p6 peptides derived from subtype A are not degraded by IDE. Thus, IDE mediated degradation of p6 is specific for HIV-1 group M isolates and not occasionally distributed among HIV-1. Full article

(This article belongs to the Section Animal Viruses)

▼ Show Figures

Figure 1

18 pages, 2569 KiB

Open AccessArticle

RVFV Infection in Goats by Different Routes of Inoculation

by Andrea L. Kroeker^1,*, Valerie Smid¹, Carissa Embury-Hyatt¹, Estella Moffat¹, Brad Collignon¹, Oliver Lung^1,2, Robbin Lindsay^3,4 and Hana Weingartl^1,5,*

¹ Canadian Food Inspection Agency, Winnipeg, MB R3E 3M4, Canada

² Department of Biological Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada

³ Public Health Agency of Canada, Winnipeg, MB R3E 3M4, Canada

⁴ Department of Entomology, University of Manitoba, Winnipeg, MB R3T 2N2, Canada

⁵ Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada

Viruses 2018, 10(12), 709; https://doi.org/10.3390/v10120709 - 12 Dec 2018

Cited by 8 | Viewed by 4709

Abstract

Rift Valley fever virus (RVFV) is a zoonotic arbovirus of the Phenuiviridae family. Infection causes abortions in pregnant animals, high mortality in neonate animals, and mild to severe symptoms in both people and animals. There is currently an ongoing effort to produce safe [...] Read more.

Rift Valley fever virus (RVFV) is a zoonotic arbovirus of the Phenuiviridae family. Infection causes abortions in pregnant animals, high mortality in neonate animals, and mild to severe symptoms in both people and animals. There is currently an ongoing effort to produce safe and efficacious veterinary vaccines against RVFV in livestock to protect against both primary infection in animals and zoonotic infections in people. To test the efficacy of these vaccines, it is essential to have a reliable challenge model in relevant target species, including ruminants. We evaluated two goat breeds (Nubian and LaMancha), three routes of inoculation (intranasal, mosquito-primed subcutaneous, and subcutaneous) using an infectious dose of 10⁷ pfu/mL, a virus strain from the 2006–2007 Kenyan/Sudan outbreak and compared the effect of using virus stocks produced in either mammalian or mosquito cells. Our results demonstrated that the highest and longest viremia titers were achieved in Nubian goats. The Nubian breed was also efficient at producing clinical signs, consistent viremia (peak viremia: 1.2 × 10³–1.0 × 10⁵ pfu/mL serum), nasal and oral shedding of viral RNA (1.5 × 10¹–8 × 10⁶ genome copies/swab), a systemic infection of tissues, and robust antibody responses regardless of the inoculation route. The Nubian goat breed and a needle-free intranasal inoculation technique could both be utilized in future vaccine and challenge studies. These studies are important for preventing the spread and outbreak of zoonotic viruses like RVFV and are supported by the Canadian-led BSL4ZNet network. Full article

(This article belongs to the Special Issue Animal Models for Viral Diseases)

▼ Show Figures

Figure 1

27 pages, 1385 KiB

Open AccessReview

Modulation of Innate Immune Responses by the Influenza A NS1 and PA-X Proteins

by Aitor Nogales^1,2,*, Luis Martinez-Sobrido¹

, David J. Topham^1,3

and Marta L. DeDiego^1,3,4,*

¹ Department of Microbiology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA

² Centro de Investigación en Sanidad Animal (CISA)-INIA, Valdeolmos, 28130 Madrid, Spain

³ David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York, NY 14642, USA

⁴ Department of Molecular and Cell Biology, Centro Nacional de Biotecnología (CNB-CSIC), Campus Universidad Autónoma de Madrid, 28049 Madrid, Spain

Viruses 2018, 10(12), 708; https://doi.org/10.3390/v10120708 - 12 Dec 2018

Cited by 74 | Viewed by 9797

Abstract

Influenza A viruses (IAV) can infect a broad range of animal hosts, including humans. In humans, IAV causes seasonal annual epidemics and occasional pandemics, representing a serious public health and economic problem, which is most effectively prevented through vaccination. The defense mechanisms that [...] Read more.

Influenza A viruses (IAV) can infect a broad range of animal hosts, including humans. In humans, IAV causes seasonal annual epidemics and occasional pandemics, representing a serious public health and economic problem, which is most effectively prevented through vaccination. The defense mechanisms that the host innate immune system provides restrict IAV replication and infection. Consequently, to successfully replicate in interferon (IFN)-competent systems, IAV has to counteract host antiviral activities, mainly the production of IFN and the activities of IFN-induced host proteins that inhibit virus replication. The IAV multifunctional proteins PA-X and NS1 are virulence factors that modulate the innate immune response and virus pathogenicity. Notably, these two viral proteins have synergistic effects in the inhibition of host protein synthesis in infected cells, although using different mechanisms of action. Moreover, the control of innate immune responses by the IAV NS1 and PA-X proteins is subject to a balance that can determine virus pathogenesis and fitness, and recent evidence shows co-evolution of these proteins in seasonal viruses, indicating that they should be monitored for enhanced virulence. Importantly, inhibition of host gene expression by the influenza NS1 and/or PA-X proteins could be explored to develop improved live-attenuated influenza vaccines (LAIV) by modulating the ability of the virus to counteract antiviral host responses. Likewise, both viral proteins represent a reasonable target for the development of new antivirals for the control of IAV infections. In this review, we summarize the role of IAV NS1 and PA-X in controlling the antiviral response during viral infection. Full article

(This article belongs to the Special Issue Cytokine Responses in Viral Infections)

▼ Show Figures

Figure 1

12 pages, 2761 KiB

Open AccessArticle

Metatranscriptomic Analysis and In Silico Approach Identified Mycoviruses in the Arbuscular Mycorrhizal Fungus Rhizophagus spp.

by Achal Neupane¹

, Chenchen Feng², Jiuhuan Feng^1,2, Arjun Kafle¹, Heike Bücking¹

and Shin-Yi Lee Marzano^1,2,*

¹ Department of Biology and Microbiology, South Dakota State University, Brookings, SD 57007, USA

² Department of Agronomy, Horticulture, and Plant Sciences, South Dakota State University, Brookings, SD 57007, USA

Viruses 2018, 10(12), 707; https://doi.org/10.3390/v10120707 - 12 Dec 2018

Cited by 21 | Viewed by 5070

Abstract

Arbuscular mycorrhizal fungi (AMF), including Rhizophagus spp., can play important roles in nutrient cycling of the rhizosphere. However, the effect of virus infection on AMF’s role in nutrient cycling cannot be determined without first knowing the diversity of the mycoviruses in AMF. Therefore, [...] Read more.

Arbuscular mycorrhizal fungi (AMF), including Rhizophagus spp., can play important roles in nutrient cycling of the rhizosphere. However, the effect of virus infection on AMF’s role in nutrient cycling cannot be determined without first knowing the diversity of the mycoviruses in AMF. Therefore, in this study, we sequenced the R. irregularis isolate-09 due to its previously demonstrated high efficiency in increasing the N/P uptake of the plant. We identified one novel mitovirus contig of 3685 bp, further confirmed by reverse transcription-PCR. Also, publicly available Rhizophagus spp. RNA-Seq data were analyzed to recover five partial virus sequences from family Narnaviridae, among which four were from R. diaphanum MUCL-43196 and one was from R. irregularis strain-C2 that was similar to members of the Mitovirus genus. These contigs coded genomes larger than the regular mitoviruses infecting pathogenic fungi and can be translated by either a mitochondrial translation code or a cytoplasmic translation code, which was also reported in previously found mitoviruses infecting mycorrhizae. The five newly identified virus sequences are comprised of functionally conserved RdRp motifs and formed two separate subclades with mitoviruses infecting Gigaspora margarita and Rhizophagus clarus, further supporting virus-host co-evolution theory. This study expands our understanding of virus diversity. Even though AMF is notably hard to investigate due to its biotrophic nature, this study demonstrates the utility of whole root metatranscriptome. Full article

(This article belongs to the Special Issue Mycoviruses)

▼ Show Figures

Figure 1

11 pages, 3410 KiB

Open AccessReview

Vertical and Horizontal Transmission of Pospiviroids

by Yosuke Matsushita^1,*

, Hironobu Yanagisawa² and Teruo Sano³

¹ Institute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization, Tsukuba, Ibaraki 305-0852, Japan

² Central Region Agricultural Research Center, National Agriculture and Food Research Organization, Tsukuba, Ibaraki 305-8666, Japan

³ Faculty of Agriculture and Life Science, Hirosaki University, Hirosaki, Aomori 036-8561, Japan

Viruses 2018, 10(12), 706; https://doi.org/10.3390/v10120706 - 12 Dec 2018

Cited by 34 | Viewed by 12565

Abstract

Viroids are highly structured, single-stranded, non-protein-coding circular RNA pathogens. Some viroids are vertically transmitted through both viroid-infected ovule and pollen. For example, potato spindle tuber viroid, a species that belongs to Pospiviroidae family, is delivered to the embryo through the ovule or pollen [...] Read more.

Viroids are highly structured, single-stranded, non-protein-coding circular RNA pathogens. Some viroids are vertically transmitted through both viroid-infected ovule and pollen. For example, potato spindle tuber viroid, a species that belongs to Pospiviroidae family, is delivered to the embryo through the ovule or pollen during the development of reproductive tissues before embryogenesis. In addition, some of Pospiviroidae are also horizontally transmitted by pollen. Tomato planta macho viroid in pollen infects to the ovary from pollen tube during pollen tube elongation and eventually causes systemic infection, resulting in the establishment of horizontal transmission. Furthermore, fertilization is not required to accomplish the horizontal transmission. In this review, we will overview the recent research progress in vertical and horizontal transmission of viroids, mainly by focusing on histopathological studies, and also discuss the impact of seed transmission on viroid dissemination and seed health. Full article

(This article belongs to the Special Issue Viroid-2018: International Conference on Viroids and Viroid-Like RNAs)

▼ Show Figures

Figure 1

28 pages, 945 KiB

Open AccessArticle

The Revisited Genome of Bacillus subtilis Bacteriophage SPP1

by Lia M. Godinho¹, Mehdi El Sadek Fadel¹, Céline Monniot², Lina Jakutyte³, Isabelle Auzat¹, Audrey Labarde¹, Karima Djacem^1,†, Leonor Oliveira¹, Rut Carballido-Lopez², Silvia Ayora⁴

and Paulo Tavares^1,*

¹ Institut de Biologie Intégrative de la Cellule (I2BC), French Alternative Energies and Atomic Energy Commission (CEA), Centre National de la Recherche Scientifique (CNRS), Univ Paris-Sud, Université Paris-Saclay, 91190 Gif-sur-Yvette, France

² MICALIS, Institut National de la Recherche Agronomique (INRA), AgroParisTech, Université Paris-Saclay, 78350 Jouy-en-Josas, France

³ Unité de Virologie Moléculaire et Structurale (VMS), CNRS, 91198 Gif-sur-Yvette, France

⁴ Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain

^† Current address: Folium Science, Unit DX, St Philips Central, Albert road, Bristol BS2 0XJ, UK.

Viruses 2018, 10(12), 705; https://doi.org/10.3390/v10120705 - 11 Dec 2018

Cited by 13 | Viewed by 6350

Abstract

Bacillus subtilis bacteriophage SPP1 is a lytic siphovirus first described 50 years ago. Its complete DNA sequence was reported in 1997. Here we present an updated annotation of the 44,016 bp SPP1 genome and its correlation to different steps of the viral multiplication [...] Read more.

Bacillus subtilis bacteriophage SPP1 is a lytic siphovirus first described 50 years ago. Its complete DNA sequence was reported in 1997. Here we present an updated annotation of the 44,016 bp SPP1 genome and its correlation to different steps of the viral multiplication process. Five early polycistronic transcriptional units encode phage DNA replication proteins and lysis functions together with less characterized, mostly non-essential, functions. Late transcription drives synthesis of proteins necessary for SPP1 viral particles assembly and for cell lysis, together with a short set of proteins of unknown function. The extensive genetic, biochemical and structural biology studies on the molecular mechanisms of SPP1 DNA replication and phage particle assembly rendered it a model system for tailed phages research. We propose SPP1 as the reference species for a new SPP1-like viruses genus of the Siphoviridae family. Full article

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

▼ Show Figures

Figure 1

17 pages, 953 KiB

Open AccessReview

Pathogen at the Gates: Human Cytomegalovirus Entry and Cell Tropism

by Christopher C. Nguyen

and Jeremy P. Kamil^*

Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA

Viruses 2018, 10(12), 704; https://doi.org/10.3390/v10120704 - 11 Dec 2018

Cited by 116 | Viewed by 10403

Abstract

The past few years have brought substantial progress toward understanding how human cytomegalovirus (HCMV) enters the remarkably wide spectrum of cell types and tissues that it infects. Neuropilin-2 and platelet-derived growth factor receptor alpha (PDGFRα) were identified as receptors, respectively, for the trimeric [...] Read more.

The past few years have brought substantial progress toward understanding how human cytomegalovirus (HCMV) enters the remarkably wide spectrum of cell types and tissues that it infects. Neuropilin-2 and platelet-derived growth factor receptor alpha (PDGFRα) were identified as receptors, respectively, for the trimeric and pentameric glycoprotein H/glycoprotein L (gH/gL) complexes that in large part govern HCMV cell tropism, while CD90 and CD147 were also found to play roles during entry. X-ray crystal structures for the proximal viral fusogen, glycoprotein B (gB), and for the pentameric gH/gL complex (pentamer) have been solved. A novel virion gH complex consisting of gH bound to UL116 instead of gL was described, and findings supporting the existence of a stable complex between gH/gL and gB were reported. Additional work indicates that the pentamer promotes a mode of cell-associated spread that resists antibody neutralization, as opposed to the trimeric gH/gL complex (trimer), which appears to be broadly required for the infectivity of cell-free virions. Finally, viral factors such as UL148 and US16 were identified that can influence the incorporation of the alternative gH/gL complexes into virions. We will review these advances and their implications for understanding HCMV entry and cell tropism. Full article

(This article belongs to the Special Issue Recent Advances in Cytomegalovirus Research)

▼ Show Figures

Figure 1

6 pages, 593 KiB

Open AccessCommunication

Complete Nucleotide Sequence of a Partitivirus from Rhizoctonia solani AG-1 IA Strain C24

by Chen Liu, Miaolin Zeng, Meiling Zhang, Canwei Shu^* and Erxun Zhou^*

Guangdong Province Key Laboratory of Microbial Signals and Disease Control, College of Agriculture, South China Agricultural University, Guangzhou 510642, China

Viruses 2018, 10(12), 703; https://doi.org/10.3390/v10120703 - 11 Dec 2018

Cited by 16 | Viewed by 3751

Abstract

The complete genome of a novel double-stranded (ds) RNA mycovirus, named as Rhizoctonia solani partitivirus 5 (RsPV5), isolated from rice sheath blight fungus R. solani AG-1 IA strain C24, was sequenced and analysed. RsPV5 consists of two segments, dsRNA-1 (1899 nucleotides) and dsRNA-2 [...] Read more.

The complete genome of a novel double-stranded (ds) RNA mycovirus, named as Rhizoctonia solani partitivirus 5 (RsPV5), isolated from rice sheath blight fungus R. solani AG-1 IA strain C24, was sequenced and analysed. RsPV5 consists of two segments, dsRNA-1 (1899 nucleotides) and dsRNA-2 (1787 nucleotides). DsRNA-1 has an open reading frame (ORF) 1 that potentially codes for a protein of 584 amino acid (aa) containing the conserved motifs of a RNA-dependent RNA polymerase (RdRp), and dsRNA-2 also contains a ORF 2, encoding a putative capsid protein (CP) of 513 aa. Phylogenetic analysis revealed that RsPV5 clustered together with six other viruses in an independent clade of the genus Alphapartitivirus, indicating that RsPV5 was a new member of the genus Alphapartitivirus, within the family Partitiviridae. Full article

(This article belongs to the Special Issue Mycoviruses)

▼ Show Figures

Figure 1

Journal Menu

Journal Browser

Viruses, Volume 10, Issue 12 (December 2018) – 71 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI