Spotlight
Structure and Assembly
Structure and AssemblyUL88 Mediates the Incorporation of a Subset of Proteins into the Virion TegumentA better understanding of the role and functions of tegument proteins in HCMV, many of which remain uncharacterized, will contribute to our understanding of the biology of HCMV. The virus has a large genome, greater than 230 kb, and functional annotation of these genes is important for identifying novel targets for improving therapeutic intervention. This study identifies a role for a viral tegument protein with unknown function, UL88,...
Genome Replication and Regulation of Viral Gene Expression
Genome Replication and Regulation of Viral Gene ExpressionKaposi’s Sarcoma-Associated Herpesvirus Fine-Tunes the Temporal Expression of Late Genes by Manipulating a Host RNA Quality Control PathwayKaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic gammaherpesvirus that causes Kaposi’s sarcoma and other lymphoproliferative disorders. Nuclear expression of KSHV genes results in exposure to at least two host-mediated nuclear RNA decay pathways, the PABPN1- and PAPα/γ-mediated RNA decay (PPD) pathway and an ARS2-mediated decay pathway. Perhaps unsurprisingly, we previously found that KSHV uses specific mechanisms to...
Genome Replication and Regulation of Viral Gene ExpressionAutonomously Replicating RNAs of Bungowannah Pestivirus: ERNS Is Not Essential for the Generation of Infectious ParticlesThe proteins NPRO and ERNS are unique for the genus Pestivirus, but only NPRO has been demonstrated to be nonessential for in vitro growth. While this was also speculated for ERNS, it has always been previously shown that pestivirus replicons with deletions of the structural proteins ERNS, E1, or E2 did not produce any infectious progeny virus in susceptible host...
Genome Replication and Regulation of Viral Gene ExpressionPhosphorylation of the Human Papillomavirus E2 Protein at Tyrosine 138 Regulates Episomal ReplicationPapillomavirus (PV) is a double-stranded DNA tumor virus infecting the cutaneous and mucosal epithelium. The PV E2 protein associates with a number of cellular factors to mediate replication of the HPV genome. Fibroblast growth factor receptor 3 (FGFR3) regulates HPV replication through phosphorylation of tyrosine 138 in the HPV E2 protein. Employing a quasivirus infection model and selection for G418 resistant genomes, we demonstrated...
Genetic Diversity and Evolution
Genetic Diversity and EvolutionGenetic Characterization of Influenza A Viruses in Japanese Swine in 2015 to 2019Understanding the current status of influenza A viruses of swine (IAVs-S) and their evolution at the farm level is important for controlling these pathogens. Efforts to monitor IAVs-S during 2015 to 2019 yielded H1N1, H1N2, and H3N2 viruses. H1 genes in Japanese swine formed a unique clade in the classical swine H1 lineage of 1A.1, and H3 genes originating from 1999–2000 human seasonal influenza viruses appear to have become established...
Virus-Cell Interactions
Virus-Cell InteractionsInfluence of Human Cytomegalovirus Glycoprotein O Polymorphism on the Inhibitory Effect of Soluble Forms of Trimer- and Pentamer-Specific Entry ReceptorsHuman cytomegalovirus (HCMV) is known for its broad cell tropism, as reflected by the different organs and tissues affected by HCMV infection. Hence, inhibition of HCMV entry into distinct cell types could be considered a promising therapeutic option to limit cell-free HCMV infection. Soluble forms of cellular entry receptor PDGFRα rather than those of entry receptor neuropilin-2 inhibit infection of multiple cell types. sPDGFRα...
Virus-Cell InteractionsMacropinocytosis and Clathrin-Dependent Endocytosis Play Pivotal Roles for the Infectious Entry of Puumala VirusThe family Hantaviridae comprises a diverse group of virus species and is considered an emerging global public health threat. Individual hantavirus species differ considerably in terms of their pathogenicity but also in their cell biology and host-pathogen interactions. In this study, we focused on the most prevalent pathogenic hantavirus in Europe, Puumala virus (PUUV), and investigated the entry and internalization of PUUV...
Virus-Cell InteractionsType I Phosphatidylinositol-4-Phosphate 5-Kinases α and γ Play a Key Role in Targeting HIV-1 Pr55Gag to the Plasma MembranePM specificity of Pr55Gag membrane binding is mediated through the interaction of PI(4,5)P2 with the matrix (MA) basic residues. It was shown that overexpression of a PI(4,5)P2-depleting enzyme strongly impaired PM localization of Pr55Gag. However, cellular factors that control PI(4,5)P2 production required for Pr55Gag-PM targeting have not yet been characterized. In this...
Virus-Cell InteractionsHenipavirus W Proteins Interact with 14-3-3 To Modulate Host Gene ExpressionNipah virus (NiV) and Hendra virus (HeV), members of the Henipavirus genus, are recently emerged, highly lethal zoonotic pathogens that cause yearly outbreaks. NiV and HeV each encode a W protein that has roles in regulating host signaling pathways, including antagonism of the innate immune response. However, the mechanisms used by W to regulate these host responses are not clear. Here, characterization of the interaction of...
Virus-Cell Interactions | SpotlightHIV-1 Exploits CLASP2 To Induce Microtubule Stabilization and Facilitate Virus Trafficking to the NucleusWhile microtubules (MTs) have long been known to be important for delivery of incoming HIV-1 cores to the nucleus, how the virus engages and exploits these filaments remains poorly understood. Our previous work revealed the importance of highly specialized MT regulators that belong to a family called plus-end tracking proteins (+TIPs) in facilitating early stages of infection. These +TIPs perform various functions, such as engaging...
Virus-Cell Interactions | SpotlightLactoferrin-Hexon Interactions Mediate CAR-Independent Adenovirus Infection of Human Respiratory CellsMany viruses enter target cells using cell adhesion molecules as receptors. Paradoxically, these molecules are abundant on the lateral and basolateral side of intact, polarized, epithelial target cells, but absent on the apical side that must be penetrated by incoming viruses to initiate infection. Our study provides a model whereby viruses use different mechanisms to infect polarized epithelial cells depending on which side of the cell...
Virus-Cell InteractionsAntiapoptotic Clone 11-Derived Peptides Induce In Vitro Death of CD4+ T Cells Susceptible to HIV-1 InfectionAlthough antiretroviral treatment efficiently blocks HIV multiplication, it cannot eliminate cells already carrying integrated proviruses. In the search for an HIV cure, the identification of new potential targets to selectively eliminate infected cells is of the outmost importance. We show here that peptides derived from antiapoptotic clone 11 (AAC-11), whose expression levels correlated with susceptibility to HIV-1 infection of CD4...
Cellular Response to Infection
Cellular Response to Infection | SpotlightConserved Herpesvirus Kinase ORF36 Activates B2 Retrotransposons during Murine Gammaherpesvirus InfectionViral infection dramatically changes the levels of many types of RNA in a cell. In particular, certain oncogenic viruses activate expression of repetitive genes called retrotransposons, which are normally silenced due to their ability to copy and spread throughout the genome. Here, we established that infection with the gammaherpesvirus MHV68 leads to a dramatic induction of a class of noncoding retrotransposons called B2 SINEs in...
Cellular Response to InfectionHerpes Simplex Virus 1 ICP34.5 Alters Mitochondrial Dynamics in NeuronsHerpes simplex virus persists lifelong in neurons and can reactivate to cause recurrent lesions in mucosal tissues. A key determinant of virulence is the viral protein ICP34.5, of which residues 68 to 87 significantly contribute to neurovirulence through an unknown mechanism. Our report provides evidence that residues 68 to 87 of ICP34.5 are required for binding mitochondrion-associated factors. These interactions alter mitochondrial...
Transformation and Oncogenesis
Transformation and OncogenesisPolyomavirus Small T Antigen Induces Apoptosis in Mammalian Cells through the UNC5B Pathway in a PP2A-Dependent MannerUNC5B, PP2A, and netrin-1 are deregulated in a variety of cancers. UNC5B and PP2A are regarded as tumor suppressors, as they promote apoptosis and are deleted or mutated in many cancers. In contrast, netrin-1 promotes survival by inhibiting dependence receptors, including UNC5B, and is upregulated in many cancers. Here, we show that UNC5B-mediated apoptosis can occur independently of p53 but in a PP2A-dependent manner. A substantial...
Vaccines and Antiviral Agents
Vaccines and Antiviral AgentsAbsence of Long-Term Protection in Domestic Pigs Immunized with Attenuated African Swine Fever Virus Isolate OURT88/3 or BeninΔMGF Correlates with Increased Levels of Regulatory T Cells and Interleukin-10The duration of immunity for any vaccine candidate is crucial. In the case of African swine fever virus vaccine candidates, this issue has received little attention. Attenuated viruses have proven protective following short immunization protocols in which pigs were challenged a few weeks after the first immunization. Here, the duration of immunity and the immune responses induced over a duration of 130 days were studied during...
Vaccines and Antiviral AgentsPolyethylene Glycol 40-Modified Peptide with High Therapeutic Efficacy in Simian-Human Immunodeficiency Virus-Acutely Infected Rhesus MonkeysPoor pharmacokinetics have severely hindered the clinical use of anti-HIV peptides. Different small molecules, such as lipid, cholesterol, and small PEG, were designed to modify peptides to improve their pharmacokinetics. In this study, we incorporated large branched PEG to anti-HIV peptide and obtained a conjugate with extended half-life and improved in vivo efficacy. The strategy we developed in this study can also be...
Vaccines and Antiviral Agents | SpotlightDesign of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic ActivityThe COVID-19 pandemic, caused by SARS-CoV-2, presents a serious global public health emergency in urgent need of prophylactic and therapeutic interventions. The S protein of coronaviruses mediates viral receptor binding and membrane fusion, thus being considered a critical target for antivirals. Herein, we report that the SARS-CoV-2 S protein has evolved a high level of activity to mediate cell-cell fusion, significantly differing from...
Pathogenesis and Immunity
Pathogenesis and ImmunityDifferential Vpu-Mediated CD4 and Tetherin Downregulation Functions among Major HIV-1 Group M SubtypesThe HIV-1 accessory protein Vpu enhances viral spread by downregulating CD4 and BST-2/tetherin on the surface of infected cells. Natural variability in these Vpu functions may contribute to HIV-1 pathogenesis, but this has not been investigated among the diverse viral subtypes that contribute to the HIV-1 pandemic. In this study, we found that Vpu function differs significantly among HIV-1 subtypes A, B, C, and D. On average, subtype C...
Pathogenesis and Immunity | SpotlightVirologic and Immunologic Features of Simian Immunodeficiency Virus Control Post-ART Interruption in Rhesus MacaquesWhile effective, antiretroviral therapy is not a cure for HIV infection. Therefore, there is great interest in achieving viral remission in the absence of antiretroviral therapy. Posttreatment controllers represent a small subset of individuals who are able to control HIV after cessation of antiretroviral therapy, but characteristics associated with these individuals have been largely limited to peripheral blood analysis. Here, we...
Pathogenesis and ImmunityAminopeptidase N Expression, Not Interferon Responses, Determines the Intestinal Segmental Tropism of Porcine DeltacoronavirusThe zoonotic potential of the PDCoV, a coronavirus efficiently infecting cells from a broad range species, including porcine, chicken, and human, emphasizes the urgent need to further study the cell and tissue tropism of PDCoV in its natural host. Herein, we generated crypt stem cell-derived enteroids from porcine different intestinal regions, which well recapitulated the events in vivo of PDCoV infection that PDCoV targeted...
Pathogenesis and ImmunityCD4 Deficiency Causes Poliomyelitis and Axonal Blebbing in Murine Coronavirus-Induced NeuroinflammationThe current trend in CNS disease biology is to attempt to understand the neural-cell–immune interaction to investigate the underlying mechanism of neuroinflammation, rather than focusing on peripheral immune activation. Most studies in MS are targeted toward understanding the involvement of CNS white matter. However, the importance of gray matter damage has become critical in understanding the long-term progressive neurological disorder...
Pathogenesis and ImmunityDelayed Expression of PD-1 and TIGIT on HIV-Specific CD8 T Cells in Untreated HLA-B*57:01 Individuals Followed from Early InfectionGiven the synergistic nature of TIGIT and PD-1, the coexpression of those inhibitory receptors should be considered when evaluating T-cell pathogenesis, developing immunomodulatory therapies or vaccines for HIV, and when using immunotherapy or vaccination for other causes in HIV-infected patients. HIV-mediated T-cell exhaustion influences the patient´s disease progression, immune system and subsequently non-AIDS complications, and...
Letter to the Editor
Authors Corrections
Masthead
NEW: COVID-19 Research & Resources from ASM
Current Issue
About JVI
Journal of Virology® (JVI) explores the nature of viruses, reporting important new discoveries and pointing to new directions in research.
For Authors
Dr. Rozanne M. Sandri-Goldin, Editor in Chief