46,544 results match your criteria Journal of Virology[Journal]


Discovery of small molecule inhibitors targeting the E3 ubiquitin ligase activity of the HSV-1 ICP0 protein using an high throughput screening assay.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

University of Kansas Medical Center, Department of Microbiology, Molecular Genetics, Immunology, 3901 Rainbow Blvd, Building Hixon, room 3009, Kansas City, KS, 66160

Herpes simplex virus-1 (HSV-1) has infected more than 80% of the population. Reactivation of the virus causes diseases ranging in severity from benign cold sores to fatal encephalitis. Current treatments involve viral DNA replication inhibitors but emergence of drug resistant mutants is observed frequently, highlighting the need for novel anti-viral therapies. Read More

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http://dx.doi.org/10.1128/JVI.00619-19DOI Listing

Oral vaccination with replication-competent adenovirus in mice reveals the dissemination of the viral vaccine beyond the gastrointestinal tract.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Dept. of Immunology and Vaccinology, Faculty of Veterinary Medicine, FARAH, University of Liège, Belgium.

Since the 1970s, replication-competent human adenoviruses 4 and 7 have been used as oral vaccines to protect US soldiers against the severe respiratory diseases caused by these viruses. These vaccines are thought to establish a digestive tract infection conferring protection against respiratory challenge through antibodies. The success of these vaccines makes replication-competent adenoviruses attractive candidates for use as oral vaccine vectors. Read More

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http://dx.doi.org/10.1128/JVI.00237-19DOI Listing

Regulation of human cytomegalovirus secondary envelopment by a C-terminal tetra-lysine motif in pUL71.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Institute of Virology, Ulm University Medical Center, 89081 Ulm, Germany.

Human cytomegalovirus (HCMV) secondary envelopment requires the viral tegument protein pUL71. Lack of pUL71 results in a complex ultrastructural phenotype with increased numbers of viral capsids undergoing envelopment at the cytoplasmic virus assembly complex. Here, we report a role of the pUL71 C-terminus in secondary envelopment. Read More

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http://dx.doi.org/10.1128/JVI.02244-18DOI Listing

Comparisons of human immunodeficiency virus type 1 envelope variants in blood and genital fluids near the time of male-to-female transmission.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA

To better understand the transmission of human immunodeficiency virus type-1 (HIV-1), the genetic characteristics of male blood and genital viruses were compared to the imputed founding virus population in their female partners. Initially serodiscordant heterosexual African couples with sequence-confirmed male-to-female HIV-1 transmission and blood and genitial specimens near the time of transmission were studied. Single viral templates from blood plasma and genital tract RNA and DNA were sequenced across HIV-1 gp160. Read More

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http://dx.doi.org/10.1128/JVI.01769-18DOI Listing

Asparagine is a critical limiting metabolite for vaccinia virus protein synthesis during glutamine deprivation.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Division of Biology, Kansas State University, Manhattan, Kansas 66506, USA

Viruses actively interact with host metabolism because viral replication relies on host cells to provide nutrients and energy. Vaccinia virus (VACV; the prototype poxvirus) prefers glutamine to glucose for efficient replication to the extent that VACV replication is hindered in glutamine-free medium. Remarkably, our data show that VACV replication can be fully rescued from glutamine depletion by asparagine supplementation. Read More

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http://dx.doi.org/10.1128/JVI.01834-18DOI Listing

Seeking closure: How do herpesviruses recruit the cellular ESCRT apparatus?

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Department of Developmental and Molecular Biology, Dominic D. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA

The Herpesviridae are structurally complex DNA viruses whose capsids undergo primary envelopment at the inner nuclear membrane and secondary envelopment at organelles in the cytoplasm. In both locations there is evidence that envelope formation and scission involve the participation of multiple viral proteins and also the cellular ESCRT apparatus. It nevertheless appears that the best understood viral strategies for ESCRT recruitment, those adopted by the retroviruses and many other families of enveloped RNA viruses, are not utilized by the Herpesviridae, at least during envelopment in the cytoplasm. Read More

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http://dx.doi.org/10.1128/JVI.00392-19DOI Listing

Phosphoproteome analysis of cells infected with adapted and non-adapted influenza A virus reveals novel pro- and antiviral signaling networks.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Institute of Biochemistry, Medical Faculty, Friedrichstrasse 24, Justus Liebig University, 35392 Giessen (Germany), Member of the German Center for Lung Research

Influenza A viruses (IAVs) quickly adapt to new environments and are well known to cross species barriers. To reveal a molecular basis for these phenomena, we compared the Ser/Thr and Tyr phosphoproteomes of murine lung epithelial cells early and late after infection with mouse-adapted SC35M virus or its non-adapted SC35 counterpart. With this analysis we identified a large set of upregulated Ser/Thr phosphorylations common to both viral genotypes, while Tyr phosphorylations showed little overlap. Read More

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http://dx.doi.org/10.1128/JVI.00528-19DOI Listing

Interplay between the epigenetic enzyme lysine (K)-specific demethylase 2B and Epstein-Barr virus infection.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

International Agency for Research on Cancer, World Health Organization, Lyon, France.

The histone modifier lysine (K)-specific demethylase 2B (KDM2B) plays a role in differentiation of hematopoietic cells, and its expression appears to be deregulated in certain cancers of hematological and lymphoid origins. We have previously found that the gene is differentially methylated in cell lines derived from Epstein-Barr virus (EBV)-associated endemic Burkitt lymphoma (eBL) compared with EBV-negative sporadic BL cells. However, whether KDM2B plays a role in eBL development has not been previously investigated. Read More

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http://dx.doi.org/10.1128/JVI.00273-19DOI Listing

Carnivore parvovirus ecology in the Serengeti ecosystem: vaccine strains circulating and new host species identified.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, USA

Carnivore parvoviruses infect wild and domestic carnivores and cross- species transmission is believed to occur. However, viral dynamics are not well understood nor the consequences to wild carnivore populations of the introduction of new strains into wild ecosystems. To clarify the ecology of these viruses in a multi-host system such as the Serengeti ecosystem and identify potential threats for wildlife conservation we analyzed, through real-time PCR, 152 samples belonging to 14 wild carnivore species and 62 samples from healthy domestic dogs. Read More

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http://dx.doi.org/10.1128/JVI.02220-18DOI Listing

Complex membrane remodeling during virion assembly of the 30,000 years-old Mollivirus sibericum.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Ultrastructural Bio-imaging (UBI), Center for ressources and research in technology (C2RT) and Department of Cell Biology and Infection, Institut Pasteur, 25-28, rue du Dr. Roux, 75015 Paris, France.

Cellular membranes ensure functional compartmentalization by dynamic fusion-fission remodeling and are often targeted by viruses during entry, replication, assembly and egress. Nucleocytoplasmic large DNA viruses (NCLDVs) can recruit host-derived open membrane precursors to form their inner viral membrane. Using complementary 3D-electron microscopy techniques including focused-ion beam scanning electron microscopy and electron tomography, we show that the giant Mollivirus sibericum utilizes the same strategy but also displays unique features. Read More

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http://jvi.asm.org/lookup/doi/10.1128/JVI.00388-19
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http://dx.doi.org/10.1128/JVI.00388-19DOI Listing
April 2019
1 Read

The reduced folate carrier: an entry receptor for a novel feline leukemia virus variant.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Laboratory of Molecular Immunology and Infectious Disease, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan

Feline leukemia virus (FeLV) is horizontally transmitted among cats and causes a variety of hematopoietic disorders. Five subgroups of FeLV, A-D and T, each with distinct receptor usage, have been described. Recently, we identified a new FeLV Env (TG35-2) gene from a pseudotyped virus that does not belong to any known subgroup. Read More

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http://dx.doi.org/10.1128/JVI.00269-19DOI Listing

A genome-wide haploid genetic screen identifies heparan sulfate-associated genes and the macropinocytosis modulator TMED10 as factors supporting vaccinia virus infection.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands

Vaccinia virus is a promising viral vaccine and gene delivery candidate, and has historically been used as a model to study poxvirus-host cell interactions. We employed a genome-wide insertional mutagenesis approach in human haploid cells to identify host factors crucial for vaccinia virus infection. A library of mutagenized HAP1 cells was exposed to Modified Vaccinia Virus Ankara (MVA). Read More

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http://dx.doi.org/10.1128/JVI.02160-18DOI Listing

Aerosol Transmission of Gull-Origin Iceland Subtype H10N7 Influenza A Virus in Ferrets.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Department of Basic Science, College of Veterinary Medicine, Mississippi State University, Mississippi, United States

Subtype H10 influenza A viruses (IAVs) have been recovered from domestic poultry and various aquatic bird species, and sporadic transmission of these IAVs from avian species to mammals (i.e., human, seal, and mink) are well documented. Read More

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http://jvi.asm.org/lookup/doi/10.1128/JVI.00282-19
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http://dx.doi.org/10.1128/JVI.00282-19DOI Listing
April 2019
1 Read

Adenovirus E1B-55K targets SMARCAL1 for degradation during infection and modulates cellular DNA replication.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Institute of Cancer & Genomic Sciences Institute of Metabolism & Systems Research; College of Medical and Dental Sciences, The University of Birmingham, United Kingdom, B15 2TT

Here we show that the cellular DNA replication protein and ATR substrate, SMARCAL1, is recruited to viral replication centres early during adenovirus infection and is then targeted in an E1B-55K/E4orf6 and Cullin Ring Ligase-dependent manner for proteasomal degradation. In this regard we have determined that SMARCAL1 is phosphorylated at S123, S129 and S173 early during infection, in an ATR- and CDK- dependent manner, and that pharmacological inhibition of ATR and CDK activities attenuates SMARCAL1 degradation. SMARCAL1 recruitment to viral replication centres was shown to be largely dependent upon SMARCAL1 association with the RPA complex, whilst Ad-induced SMARCAL1 phosphorylation also contributed towards SMARCAL1 recruitment to viral replication centres, albeit to a limited extent. Read More

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http://dx.doi.org/10.1128/JVI.00402-19DOI Listing

Phenotypic and functional differences between HHV-6 and HCMV specific T-cells.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

INSERM 1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, F-75013, Paris, France

: Human herpesvirus 6 (HHV-6) infects over 90% of the population, and establishes a latent infection, with asymptomatic episodes of reactivation. However, HHV-6 reactivation is associated with morbidity and sometimes mortality in immunocompromised patients. To date, the control of the virus in healthy virus carriers and its failure in patients with disease remain poorly understood. Read More

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http://dx.doi.org/10.1128/JVI.02321-18DOI Listing

Cellular DNAJA3, a Novel VP1-Interacting Protein, Inhibits Foot-and-Mouth Disease Virus Replication by Inducing Lysosomal degradation of VP1 and Attenuating its Antagonistic Role on the IFN-β signaling pathway.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, Gansu, China

DnaJ Heat Shock Protein Family (Hsp40) Member A3 (DNAJA3) plays an important role in viral infections. However, the role of DNAJA3 in replication of foot-and-mouth-disease virus (FMDV) remains unknown. In this study, DNAJA3, a novel binding partner of VP1, was identified using yeast two-hybrid screening. Read More

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http://dx.doi.org/10.1128/JVI.00588-19DOI Listing

Fundamental contribution and host range determination of ANP32A and ANP32B in influenza A virus polymerase activity.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, the Chinese Academy of Agricultural Sciences, Harbin 150069, China

The polymerase of the influenza virus is part of the key machinery necessary for viral replication. However, the avian influenza virus polymerase is restricted in mammalian cells. The cellular protein ANP32A has been recently found to interact with viral polymerase, and to both influence polymerase activity and interspecies restriction. Read More

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http://dx.doi.org/10.1128/JVI.00174-19DOI Listing

Enterovirus A71 Containing Codon-Deoptimized VP1 and High-Fidelity Polymerase as Next Generation Vaccine Candidate.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Enterovirus A71 (EV-A71) is the major pathogen which causes hand-foot-and-mouth disease (HFMD) which occasionally results in severe neurological complications. In this study, we developed four EV-A71 (rgEV-A71) strains by reverse genetics procedures as possible vaccine candidates. The four rgEV-A71 viruses contained various codon deoptimized VP1 capsid protein (VP1-CD) showed similar replication rate and antigenicity to wild-type virus, while a fifth virus, rg4643C4VP-CD, was unable to form plaques, but was still able to examined by TCID50 titers which were similar to the others, thus indicating the effect of CD on plaque formation. Read More

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http://dx.doi.org/10.1128/JVI.02308-18DOI Listing

Phosphorylation of HPV-16 L2 Contributes To Efficient Virus Infectious Entry.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Tumour Virology Laboratory, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy

The Human Papillomavirus (HPV) capsid comprises two viral proteins, L1 and L2, with the L2 component being essential to ensure efficient endocytic transport of incoming viral genomes. Several studies have previously reported that L1 and L2 are post-translationally modified, but it is uncertain whether these modifications affect HPV infectious entry. Using a proteomic screen, we identified a highly conserved phospho-acceptor site on the HPV-16 and BPV-1 L2 proteins. Read More

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http://dx.doi.org/10.1128/JVI.00128-19DOI Listing

The CCCTC binding factor, CTRL2, modulates heterochromatin deposition and the establishment of HSV-1 latency .

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana

The cellular insulator protein CTCF plays a role in HSV-1 latency through the establishment and regulation of chromatin boundaries. We previously found that the CTRL2 regulatory element downstream from the LAT enhancer was bound by CTCF during latency and underwent CTCF eviction at early times post-reactivation in mice latent with 17+. We also showed that CTRL2 was a functional enhancer-blocking insulator in both epithelial and neuronal cell lines. Read More

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http://dx.doi.org/10.1128/JVI.00415-19DOI Listing

Senecavirus-Specific Recombination Assays Reveal the Intimate Link between Polymerase Fidelity and RNA Recombination.

J Virol 2019 Apr 17. Epub 2019 Apr 17.

Division of Livestock Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, No. 678 Haping Road, Xiangfang District, Harbin 150069, P. R. China.

Senecavirus A (SVA) is a re-emerging virus and recent evidence has emphasized the importance of SVA recombination on virus evolution. In this study, we report the development of an infectious cDNA clone for the SVA/HLJ/CHA/2016 strain. We have used this strain to develop a reporter virus expressing eGFP, which we then used to screen for a recombination-deficient SVA by an eGFP-retention assay. Read More

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http://dx.doi.org/10.1128/JVI.00576-19DOI Listing

Characterization of Novel Reoviruses [Wad Medani virus (Orbivirus) and Kundal (Coltivirus)] collected from ticks in India during CCHF surveillance.

J Virol 2019 Apr 10. Epub 2019 Apr 10.

ICMR-National Institute of Virology, Pune, India

In 2011, ticks were collected from livestock following an outbreak of Crimean Congo Hemorrhagic fever (CCHF) in Gujarat state, India. CCHF-negative tick pools were passaged for virus isolation, and two virus isolates were obtained, designated Karyana virus (KARYV) and Kundal virus (KUNDV) respectively. Traditional RT-PCR identification of known viruses was unsuccessful, but a next-generation sequencing approach identified KARYV and KUNDV as viruses in the family, , and genera, respectively. Read More

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http://dx.doi.org/10.1128/JVI.00106-19DOI Listing
April 2019
1 Read

NeSt1 protein enhances Zika virus pathogenesis by activating neutrophils.

J Virol 2019 Apr 10. Epub 2019 Apr 10.

Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06520, USA.

Saliva from the mosquito vector of flaviviruses is capable of changing the local immune environment, leading to an increase of flavivirus-susceptible cells at the infected bite site. Additionally, an antibody response towards specific salivary gland (SG) components changes the pathogenesis of flavivirus in human populations. To investigate if antigenic SG proteins are capable of enhancing Zika virus (ZIKV) infection, a re-emerging flavivirus primarily transmitted by the mosquito, we screened for antigenic SG proteins using a yeast display library, and demonstrate a previously undescribed SG protein, we term neutrophil stimulating factor 1 (NeSt1), activates primary mouse neutrophils Passive immunization against NeSt1 decreases pro-IL-1β and CXCL2 expression, prevents macrophages from infiltrating into the bite site, protects susceptible IFNARIFNGR (AG129) mice from early ZIKV replication, and ameliorates viral-induced pathogenesis. Read More

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http://dx.doi.org/10.1128/JVI.00395-19DOI Listing

Replication of Marek's Disease Virus is dependent on synthesis of Fatty Acid and Prostaglandin E2.

J Virol 2019 Apr 10. Epub 2019 Apr 10.

The Pirbright Institute, Ash Rd, Pirbright, Woking, GU24 0NF, UK

Marek's disease virus (MDV) causes deadly lymphoma and induces an imbalance of the lipid metabolism in infected chickens. Here, we discovered that MDV activates fatty acid synthesis (FAS) pathway in primary chicken embryo fibroblasts (CEF). In addition, MDV infected cells contained high levels of fatty acids and showed an increased numbers of lipid droplets (LDs). Read More

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http://dx.doi.org/10.1128/JVI.00352-19DOI Listing

Nipah and Hendra viral glycoproteins induce comparable homologous but distinct heterologous fusion phenotypes.

J Virol 2019 Apr 10. Epub 2019 Apr 10.

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850

Nipah and Hendra viruses (NiV and HeV) exhibit high lethality in humans and are BSL-4 paramyxoviruses in the growing genus, The attachment (G) and fusion (F) envelope glycoproteins are both required for viral entry into cells and for cell-cell fusion, pathognomonic of henipaviral infections. Here we compared the fusogenic capacities between homologous and heterologous pairs of NiV and HeV glycoproteins. Importantly, to accurately measure their fusogenic capacities, as these depend on glycoprotein cell surface expression (CSE) levels, we inserted identical extracellular tags to both fusion (FLAG tags) or both attachment (HA tags) glycoproteins. Read More

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http://dx.doi.org/10.1128/JVI.00577-19DOI Listing

Mechanisms of B-cell oncogenesis induced by Epstein-Barr virus.

J Virol 2019 Apr 10. Epub 2019 Apr 10.

Department of Otorhinolaryngology-Head and Neck Surgery, and the Tumor Virology Program, Abramson Comprehensive Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA-19104, USA

Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus, which asymptomatically infects majority of the world population. In immune-compromised conditions, EBV can trigger human cancers of epithelial and lymphoid origin. The oncogenic potential of EBV is demonstrated by infection and transformation of quiescent B-cells into lymphoblastoid cell lines (LCLs). Read More

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http://dx.doi.org/10.1128/JVI.00238-19DOI Listing

Characterizing a murine model for astrovirus using viral isolates from persistently infected immunocompromised mice.

J Virol 2019 Apr 10. Epub 2019 Apr 10.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA

Human astroviruses are single-stranded enteric RNA viruses that cause a spectrum of disease ranging from asymptomatic infection to systemic extra-gastrointestinal spread; however, they are among the least characterized enteric viruses and there is a lack of a well-characterized small animal model. Finding that immunocompromised mice were resistant to human astrovirus infection via multiple routes of inoculation, our studies aimed to determine whether murine astrovirus (MuAstV) could be used to model human astrovirus disease. We experimentally infected wildtype mice with MuAstV isolated from immunocompromised mice and found that the virus was detected throughout the gastrointestinal tract, including the stomach, but was not associated with diarrhea. Read More

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http://dx.doi.org/10.1128/JVI.00223-19DOI Listing

Antagonizing the glucocorticoid receptor impairs explant-induced reactivation in mice latently infected with herpes simplex virus 1.

J Virol 2019 Apr 10. Epub 2019 Apr 10.

Oklahoma State University, Center for Veterinary Health Sciences, Department of Veterinary Pathobiology, Stillwater, OK 74078

Herpes simplex virus 1 (HSV-1) establishes life-long latent infections in neurons. Reactivation from latency can lead to serious recurrent disease, including stromal keratitis, corneal scarring, blindness, and encephalitis. Although numerous studies link stress to an increase in the incidence of reactivation from latency and recurrent disease, the mechanism of action is not well understood. Read More

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http://dx.doi.org/10.1128/JVI.00418-19DOI Listing
April 2019
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Specific activation of HIV-1 by a bromodomain inhibitor from monocytic cells in humanized mice under ART in vivo.

J Virol 2019 Apr 10. Epub 2019 Apr 10.

Lineberger Comprehensive Cancer Center Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

The combination antiretroviral therapy (cART) effectively suppresses HIV-1 replication and enables HIV-infected individuals to live long productive lives. However, the persistence of HIV-1 reservoirs of both T and myeloid cells with latent or low-replicating HIV-1 in patients under cART makes HIV-1 infection an incurable disease. Recent studies have focused on the development of strategies to activate and purge these reservoirs. Read More

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http://dx.doi.org/10.1128/JVI.00233-19DOI Listing
April 2019
1 Read

Human papillomavirus type 11 early protein E6 activates autophagy by repressing AKT/mTOR and Erk/mTOR.

J Virol 2019 Apr 10. Epub 2019 Apr 10.

Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China

Low-risk human papillomaviruses (LR-HPVs) are the causative agents of genital warts, which is a widespread sexually transmitted disease. How LR-HPVs affect autophagy and the specific proteins involved are unknown. In the current study, we investigated the impact of LR-HPV type 11 early protein 6 (E6) on the activity of the autophagy pathway. Read More

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http://dx.doi.org/10.1128/JVI.00172-19DOI Listing

Effects of the SOS (A501C/T605C) and DS (I201C/A433C) Disulfide Bonds on HIV-1 Membrane Envelope Glycoprotein Conformation and Function.

J Virol 2019 Apr 3. Epub 2019 Apr 3.

Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Department of Microbiology, Harvard Medical School, Boston, MA 02215

Most broadly neutralizing antibodies and many entry inhibitors target the pre-triggered (State-1) conformation of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env). Here we examine two published Env mutants designed to stabilize this conformation by the introduction of artificial disulfide bonds: A501C/T605C (called SOS) and I201C/A433C (called DS). SOS Env supported virus entry and cell-cell fusion only after exposure to a reducing agent, dithiothreitol (DTT). Read More

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http://dx.doi.org/10.1128/JVI.00304-19DOI Listing
April 2019
1 Read

Histone deacetylase inhibitor SAHA suppresses human adenovirus gene expression and replication.

J Virol 2019 Apr 3. Epub 2019 Apr 3.

Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

Human adenovirus (HAdV) causes minor illnesses in most patients, but can lead to severe disease and death in pediatric, geriatric and immunocompromised individuals. No approved antiviral therapy currently exists for the treatment of these severe HAdV-induced diseases. In this study, we show that the pan-histone deacetylase (HDAC) inhibitor SAHA reduces HAdV-5 gene expression and DNA replication in tissue culture, ultimately decreasing virus yield from infected cells. Read More

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http://jvi.asm.org/lookup/doi/10.1128/JVI.00088-19
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http://dx.doi.org/10.1128/JVI.00088-19DOI Listing
April 2019
3 Reads

Arterivirus nsp4 antagonizes interferon-β production by proteolytically cleaving NEMO at multiple sites.

J Virol 2019 Apr 3. Epub 2019 Apr 3.

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

Equine arteritis virus (EAV) and porcine reproductive and respiratory syndrome virus (PRRSV) represent two members of the family and pose major threats for the horse- and swine-breeding industries worldwide. A previous study suggested that PRRSV nsp4, a 3C-like protease, antagonizes interferon (IFN)-β production by cleaving the NF-κB essential modulator (NEMO) at a single site, glutamate 349 (E349). Herein, we demonstrated that EAV nsp4 also inhibited virus-induced IFN-β production by targeting NEMO for proteolytic cleavage, and that the scission occurred at four sites- E166, E171, glutamine 205 (Q205), and E349. Read More

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http://dx.doi.org/10.1128/JVI.00385-19DOI Listing
April 2019
3 Reads

Zika Virus Subverts Stress Granules to Promote and Restrict Viral Gene Expression.

J Virol 2019 Apr 3. Epub 2019 Apr 3.

Department of Biological Sciences, The RNA Institute, University at Albany-SUNY, Albany, NY 12222

Flaviviruses limit the cell stress response by preventing the formation of stress granules and modulate viral gene expression by subverting different proteins involved in the stress granule pathway. In this study, we investigated the formation of stress granules during Zika virus (ZIKV) infection and the role stress granule proteins play during the viral life cycle. Using immunofluorescence and confocal microscopy, we determined that ZIKV disrupted the formation of arsenite-induced stress granules and changed the subcellular distribution, but not the abundance or integrity, of stress granule proteins. Read More

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http://dx.doi.org/10.1128/JVI.00520-19DOI Listing

Development of Influenza B Universal Vaccine Candidates using the "Mosaic" Hemagglutinin Approach.

J Virol 2019 Apr 3. Epub 2019 Apr 3.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Influenza B viruses cause seasonal epidemics and are a considerable burden to public health. However, protection by current seasonal vaccines is suboptimal due to the antigenic changes of the circulating strains. In this study, we report a novel universal influenza B virus vaccination strategy based on mosaic hemagglutinins. Read More

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http://dx.doi.org/10.1128/JVI.00333-19DOI Listing

C19ORF66 broadly escapes viral-induced endonuclease cleavage and restricts Kaposi's Sarcoma Associated Herpesvirus (KSHV).

J Virol 2019 Apr 3. Epub 2019 Apr 3.

Microbiology department, University of Massachusetts, Amherst

One striking characteristic of certain herpesviruses is their ability to induce rapid and widespread RNA decay in order to gain access to host resources. This phenotype is induced by viral endoribonucleases, including SOX in KSHV, muSOX in MHV68, BGLF5 in EBV and vhs in HSV-1. Here, we performed comparative RNA-seq upon expression of these herpesviral endonucleases in order to characterize their effect on the host transcriptome. Read More

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http://dx.doi.org/10.1128/JVI.00373-19DOI Listing

Envelope protein glycosylation mediates Zika virus pathogenesis.

J Virol 2019 Apr 3. Epub 2019 Apr 3.

Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus. Recent ZIKV outbreaks have produced serious human disease, including neurodevelopmental malformations (congenital Zika syndrome) and Guillain-Barré syndrome. These outcomes were not associated with ZIKV infection prior to 2013, raising the possibility that viral genetic changes could contribute to new clinical manifestations. Read More

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http://jvi.asm.org/lookup/doi/10.1128/JVI.00113-19
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http://dx.doi.org/10.1128/JVI.00113-19DOI Listing
April 2019
3 Reads

Reconstruction of the genetic history and the current spread of HIV-1 subtype A in Germany.

J Virol 2019 Apr 3. Epub 2019 Apr 3.

Division of HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany

HIV-1 non-B infections have been increasing in Europe for several years. In Germany, subtype A belongs to the most abundant non-B subtypes showing an increasing prevalence of 8.3% among new infections in 2016. Read More

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http://dx.doi.org/10.1128/JVI.02238-18DOI Listing
April 2019
4 Reads

Glucosylceramidase Maintains Influenza Infection By Regulating Endocytosis.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Department of Pathology, University of Virginia, Charlottesville, VA, USA

Influenza is an RNA virus encapsulated in a lipid bilayer derived from the host cell plasma membrane. Previous studies showed that influenza infection depends on cellular lipids including the sphingolipids sphingomyelin and sphingosine. Here we examined the role of a third sphingolipid, glucosylceramide, in influenza infection following CRISPR/Cas9-mediated knockout of its metabolizing enzyme glucosylceramidase (GBA). Read More

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http://dx.doi.org/10.1128/JVI.00017-19DOI Listing
March 2019
1 Read

African swine fever virus Armenia/07 virulent strain controls IFN-β production through cGAS-STING pathway.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Centro de Biología Molecular Severo Ochoa. CSIC-UAM. Universidad Autónoma de Madrid, 28049 Madrid, Spain.

African swine fever virus (ASFV) is a complex, cytoplasmic dsDNA virus, currently expanding throughout the world. Currently circulating virulent genotype II Armenia/07-like viruses causes fatal disease in pigs and wild boar, whereas attenuated strains induce infections with varying levels of chronic illness.Sensing cytosolic dsDNA, mainly by the key DNA sensor cGAS, leads to the synthesis of type I interferon, and involves signaling through STING, TBK1 and IRF3. Read More

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http://dx.doi.org/10.1128/JVI.02298-18DOI Listing

Voltage-dependent anion channel protein 2 (VDAC2) and receptor of activated protein C kinase 1 (RACK1) act as functional receptors for lymphocystis disease virus infection.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Laboratory of Pathology and Immunology of Aquatic Animals, KLMME, Ocean University of China, Qingdao 266003, P. R. China.

In previous researches a 27.8 kDa protein in flounder gill (FG) cells was identified as putative cellular receptor (27.8R), which mediated lymphocystis disease virus (LCDV) infection via interaction with a 32 kDa viral attachment protein (VAP) of LCDV, monoclonal antibodies (MAbs) against 27. Read More

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http://dx.doi.org/10.1128/JVI.00122-19DOI Listing

Identification of CP77 as the third orthopoxvirus SAMD9 and SAMD9L inhibitor with a unique specificity for a rodent SAMD9L.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA

Orthopoxviruses (OPXVs) have a broad host range in mammalian cells, but Chinese hamster ovary (CHO) cells are non-permissive for vaccinia virus (VACV). Here, we revealed a species-specific difference in host restriction factor SAMD9L as the cause for the restriction and identified orthopoxvirus CP77 as a unique inhibitor capable of antagonizing Chinese hamster SAMD9L (chSAMD9L). Two known VACV inhibitors of SAMD9 and SAMD9L (SAMD9&L);, K1 and C7, can bind human and mouse SAMD9&L;, but neither can bind chSAMD9L. Read More

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http://dx.doi.org/10.1128/JVI.00225-19DOI Listing
March 2019
1 Read

Intra-host Selection Pressure Drives Equine Arteritis Virus Evolution during Persistent Infection in the Stallion Reproductive Tract.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY, USA

Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a reproductive and respiratory disease of horses. Following natural infection, 10-70% of infected stallions can become carriers of EAV and continue to shed virus in the semen. In this study, sequential viruses isolated from nasal secretions, buffy coat cells and semen of seven experimentally infected and two naturally infected EAV carrier stallions were deep sequenced to elucidate the intra-host microevolutionary process after a single transmission event. Read More

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http://dx.doi.org/10.1128/JVI.00045-19DOI Listing
March 2019
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Analysis of coronavirus temperature-sensitive mutants reveals an interplay between the macrodomain and papain-like protease impacting replication and pathogenesis.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Department of Microbiology and Immunology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153

Analysis of temperature-sensitive (ts) mutant viruses is a classic method allowing researchers to identify genetic loci involved in viral replication and pathogenesis. Here, we report genetic analysis of a ts strain of mouse hepatitis virus (MHV), tsNC11, focusing on the role of mutations in the macrodomain and the papain-like protease 2 (PLP2) domain of nonstructural protein 3, a component of the viral replication complex. Using MHV reverse genetics, we generated a series of mutant viruses to define the contribution of macrodomain- and PLP2-specific mutations to the ts phenotype. Read More

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http://dx.doi.org/10.1128/JVI.02140-18DOI Listing
March 2019
12 Reads

Interferon Gamma Inhibits Varicella-Zoster Virus Replication in a Cell Line-Dependent Manner.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Department of Microbiology and Immunology, and Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932

The major immediate-early IE62 protein of varicella-zoster virus (VZV) is delivered to newly infected cell nuclei, where it initiates VZV replication by transactivating viral immediate-early (IE), early (E), and late (L) genes. Interferon gamma (IFN-γ) is a potent cytokine produced following primary VZV infection. Furthermore, VZV reactivation correlates with a decline in IFN-γ-producing immune cells. Read More

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http://dx.doi.org/10.1128/JVI.00257-19DOI Listing
March 2019
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High-throughput Screening and Identification of Potent Broad-spectrum Inhibitors of Coronaviruses.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

NHC Key Laboratory of Biosafety, Ministry of Health, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China

Coronaviruses (CoVs) act as cross-species viruses and have the potential to spread rapidly into new host species and cause epidemic diseases. Despite the severe public health threat of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome CoV (MERS-CoV), there are currently no drugs available for their treatment; therefore, broad-spectrum inhibitors of emerging and endemic CoVs are urgently needed. To search for effective inhibitory agents, we performed high-throughput screening (HTS) of a 2,000-compound library of approved drugs and pharmacologically active compounds using the established genetically engineered human CoV OC43 (HCoV-OC43) strain expressing luciferase (rOC43-ns2Del-Rluc) and validated the inhibitors using multiple genetically distinct CoVs We screened 56 hits from the HTS data and validated 36 compounds using wild-type HCoV-OC43. Read More

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http://dx.doi.org/10.1128/JVI.00023-19DOI Listing
March 2019
8 Reads

By binding CD80 and CD86, the vaccinia virus' M2 protein blocks their interactions with both CD28 and CTLA4 and potentiates CD80's binding to PD-L1.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Transgene S. A., Boulevard Gonthier d'Andernach, 67405 Illkirch-Graffenstaden - France.

In this article we report that the M2 protein encoded by the vaccinia virus is secreted as a homo-oligomer by infected cells and binds two central co-stimulation molecules: CD80 (B7-1) and CD86 (B7-2). These interactions block the ligation of the two B7 proteins to both soluble CD28 and soluble CTLA4, but favor the binding of soluble PD-L1 to soluble CD80. M2L gene orthologues are found in several other poxviruses and the B7/CD28-CTLA4 blocking activity has been identified for several culture supernatants of orthopoxvirus infected cells and for recombinant myxoma virus M2 protein homolog ( Gp120LP). Read More

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http://dx.doi.org/10.1128/JVI.00207-19DOI Listing
March 2019
1 Read

Modeling HIV-1 latency using primary CD4 T cells from HIV-1 infected ART suppressed individuals.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD

The small frequency of latently HIV-infected cells limits the testing of potential HIV cure strategies using cells from successfully suppressed individuals. To date, primary cell models of latency use cells infected Primary CD4 T cell models carrying an individual's endogenous HIV reservoir that recapitulate conditions of HIV latency are still outstanding. We developed a primary CD4 T cell model of HIV latency derived from memory CD4 T cells isolated from virally suppressed HIV-infected individuals, that recapitulates HIV-1 latency and viral reactivation events. Read More

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http://dx.doi.org/10.1128/JVI.02248-18DOI Listing
March 2019
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Oxazole-benzenesulfonamide derivatives inhibit HIV-1 reverse transcriptase interaction with cellular eEF1A and reduce viral replication.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Herston, Qld, 4029, Australia

HIV-1 replication requires direct interaction between HIV-1 reverse transcriptase (RT) and cellular eukaryotic translation elongation factor 1A (eEF1A). Our previous work showed that disrupting this interaction inhibited HIV-1 uncoating, reverse transcription and replication, indicating its potential as an anti-HIV-1 target. Here we develop a sensitive, live-cell split luciferase complementation assay (NanoBiT) to quantitatively measure inhibition of HIV-1 RT interacting with eEF1A. Read More

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http://dx.doi.org/10.1128/JVI.00239-19DOI Listing
March 2019
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Identification and characterization of a human coronavirus 229E nonstructural protein 8-associated RNA 3'-terminal adenylyltransferase activity.

J Virol 2019 Mar 27. Epub 2019 Mar 27.

Institute of Medical Virology, Justus Liebig University Giessen, Giessen, Germany

Coronavirus nonstructural protein (nsp) 8 has been suggested to have diverse activities, including 'noncanonical' template-dependent polymerase activities. Here, we characterized a recombinant form of the human coronavirus 229E (HCoV-229E) nsp8 and found that the protein has metal ion-dependent RNA 3'-terminal adenylyltransferase (TATase) activity, while other nucleotides were not (or very inefficiently) transferred to the 3' ends of single-stranded and (fully) double-stranded acceptor RNAs, respectively. Using partially double-stranded RNAs, very efficient TATase activity was observed if the opposite (template) strand contained a short 5' oligo(U) sequence while very little (if any) activity was detected for substrates with other homopolymeric or heteropolymeric sequences in the 5' overhang. Read More

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http://dx.doi.org/10.1128/JVI.00291-19DOI Listing