Spotlight
Structure and Assembly
Structure and AssemblyReovirus Пѓ1 Conformational Flexibility Modulates the Efficiency of Host Cell AttachmentNonenveloped virus entry is an incompletely understood process. For reovirus, the functional significance of conformational rearrangements in the attachment protein, Пѓ1, that occur during entry and particle uncoating are unknown. We engineered and characterized reoviruses containing cysteine mutations that cross-link Пѓ1 monomers in nonreducing conditions. We found that the introduction of a cysteine pair in the receptor-binding domain...
Structure and Assembly | SpotlightBiophysical and Dynamic Characterization of Fine-Tuned Binding of the Human Respiratory Syncytial Virus M2-1 Core Domain to Long RNAsThe main outcome is the molecular description of the fine-tuned binding of the cdM2-1/RNA complex and the provision of evidence that the domain alone has unfolding activity for long RNAs. This binding mode is essential in the understanding of the function in the full-length protein. Human respiratory syncytial virus (hRSV), an orthopneumovirus, stands out for the unique role of its M2-1 protein as a transcriptional antitermination...
Structure and AssemblyAcidic pH-Induced Conformational Changes in Chikungunya Virus Fusion Protein E1: a Spring-Twisted Region in the Domain I-III Linker Acts as a Hinge Point for Swiveling Motion of DomainsAedes mosquito-transmitted viruses such as the Zika, dengue, and chikungunya viruses have spread globally. CHIKV, similar to many other enveloped viruses, enters cells in sequential steps: step 1 involves receptor binding followed by endocytosis, and step 2 involves viral-cell membrane fusion in the endocytic vesicle. The viral envelope surface protein, E1, performs membrane fusion. E1 is triggered to undergo conformational...
Structure and AssemblyBroad-Spectrum Antiviral Entry Inhibition by Interfacially Active PeptidesNew classes of antiviral drugs are needed to treat the ever-changing viral disease landscape. Current antiviral drugs treat only a small number of viral diseases, leaving many patients with established or emerging infections to be treated solely with supportive care. Recent antiviral peptide research has produced numerous membrane-interacting peptides that inhibit diverse enveloped viruses in vitro and in vivo. Peptide...
Genome Replication and Regulation of Viral Gene Expression
Genome Replication and Regulation of Viral Gene Expression | SpotlightThe Enzymatic Activity of the nsp14 Exoribonuclease Is Critical for Replication of MERS-CoV and SARS-CoV-2The bifunctional nsp14 subunit of the coronavirus replicase contains 3′-to-5′ exoribonuclease (ExoN) and guanine-N7-methyltransferase domains. For the betacoronaviruses MHV and SARS-CoV, ExoN was reported to promote the fidelity of genome replication, presumably by mediating a form of proofreading. For these viruses, ExoN knockout mutants are viable while displaying an increased mutation frequency. Strikingly, we have now established...
Genetic Diversity and Evolution
Genetic Diversity and EvolutionComparative Circulation Dynamics of the Five Main HIV Types in ChinaWhile traditional epidemiological studies are of great interest in describing the dynamics of epidemics, they struggle to fully capture the geospatial dynamics and factors driving the dispersal of pathogens like HIV as they have difficulties capturing linkages between infections. To overcome this, we used a discrete phylogeographic approach coupled to a generalized linear model extension to characterize the dynamics and drivers of the...
Virus-Cell Interactions
Virus-Cell InteractionsSphingomyelin Is Essential for the Structure and Function of the Double-Membrane Vesicles in Hepatitis C Virus RNA Replication FactoriesPrevious reports assumed that sphingomyelin (SM) is essential for HCV replication, but the mechanism was unclear. In this study, we showed for the first time that SM and ceramide transfer protein (CERT), which is in the SM biosynthesis pathway, are essential for the biosynthesis of double-membrane vesicles (DMVs), the sites of viral replication. Low numbers of DMVs were observed in CERT-KO cells transfected with replicon RNA or with...
Virus-Cell Interactions | SpotlightCharacterization of the Herpes Simplex Virus (HSV) Tegument Proteins That Bind to gE/gI and US9, Which Promote Assembly of HSV and Transport into Neuronal AxonsHerpes simplex viruses 1 and 2 and varicella-zoster virus cause significant morbidity and mortality. One basic property of these viruses is the capacity to establish latency in the sensory neurons and to reactivate from latency and then cause disease in peripheral tissues, such as skin and mucosal epithelia. The transport of nascent HSV particles from neuron cell bodies into axons and along axons to axon tips in the periphery is an...
Virus-Cell InteractionsInositol-Requiring Enzyme 1О± Promotes Zika Virus Infection through Regulation of Stearoyl Coenzyme A Desaturase 1-Mediated Lipid MetabolismZika virus (ZIKV) has been linked to serious neurologic disorders and causes widespread concern in the field of global public health. Inositol requiring enzyme 1О± (IRE1О±) is an ER-related transmembrane protein that mediates unfolded protein response (UPR) pathway. Here, we revealed that IRE1О± is a proviral factor for ZIKV replication both in culture cells and mice model, which relies on its kinase and RNase activities. Importantly, we...
Virus-Cell InteractionsElucidating the Basis for Permissivity of the MT-4 T-Cell Line to Replication of an HIV-1 Mutant Lacking the gp41 Cytoplasmic TailThe HIV-1 Env cytoplasmic tail (CT) is required for efficient Env incorporation into nascent particles and viral transmission in primary CD4+ T cells. The MT-4 T-cell line has been reported to support multiple rounds of infection of HIV-1 encoding a gp41 CT truncation. Uncovering the underlying mechanism of MT-4 T-cell line permissivity to gp41 CT truncation would provide key insights into the role of the gp41 CT in HIV-1...
Virus-Cell InteractionsCell Type-Dependent Escape of Capsid Inhibitors by Simian Immunodeficiency Virus SIVcpzHIV-1 originated from SIVcpzPtt but not from the related virus SIVcpzPts, and thus, it is important to describe molecular infection by SIVcpzPts in human cells to understand the zoonosis of SIVs. Pharmacological HIV-1 capsid inhibitors (e.g., PF74) bind a capsid groove that is also a binding site for the cellular protein CPSF6. SIVcpzPts was resistant to PF74 in HeLa cells but sensitive in HOS cells, thus indicating cell line-specific...
Virus-Cell Interactions | SpotlightType I Interferon Susceptibility Distinguishes SARS-CoV-2 from SARS-CoVWith the ongoing outbreak of COVID-19, differences between SARS-CoV-2 and the original SARS-CoV could be leveraged to inform disease progression and eventual treatment options. In addition, these findings could have key implications for animal model development as well as further research into how SARS-CoV-2 modulates the type I IFN response early during infection.
Virus-Cell InteractionsDevelopment of Styrene Maleic Acid Lipid Particles as a Tool for Studies of Phage-Host InteractionsBacteriophages (viruses that infect bacteria or phages) impact every microbial community. All phage infections start with the binding of the viral particle to a specific receptor molecule on the host cell surface. Due to its importance in phage infections, this first step is of interest to many phage-related research and applications. However, many phage receptors are difficult to isolate. Styrene maleic acid lipid particles (SMALPs)...
Virus-Cell InteractionsCovalent Modifications of the Bacteriophage Genome Confer a Degree of Resistance to Bacterial CRISPR SystemsRestriction-modification (R-M) and CRISPR-Cas systems are two well-known defense mechanisms of bacteria. Both recognize and cleave phage DNA at specific sites while protecting their own genomes. It is well accepted that T4 and other phages have evolved counterdefense mechanisms to protect their genomes from R-M cleavage by covalent modifications, such as the hydroxymethylation and glucosylation of cytosine. However, it is unclear...
Virus-Cell InteractionsSwine MicroRNAs ssc-miR-221-3p and ssc-miR-222 Restrict the Cross-Species Infection of Avian Influenza VirusThe host range of an influenza A virus is determined by species-specific interactions between virus and host cell factors. Host miRNAs can regulate influenza A virus replication; however, the role of miRNAs in host species specificity is unclear. Here, we show that the induced expression of ssc-miR-221-3p and ssc-miR-222 in swine cells is modulated by NF-ОєB P65 phosphorylation in response to AIV infection but not swine...
Virus-Cell InteractionsGeneration of Genetically RGD Пѓ1-Modified Oncolytic Reovirus That Enhances JAM-A-Independent Infection of Tumor CellsOncolytic viruses kill tumors without affecting normal cells. A variety of oncolytic viruses are used as cancer therapeutics. Mammalian reovirus (MRV), which belongs to the genus Orthoreovirus, family Reoviridae, is one such natural oncolytic virus. The anticancer effects of MRV are being evaluated in clinical trials. Unlike other oncolytic viruses, MRV has not been genetically modified for use as a cancer therapeutic...
Cellular Response to Infection
Cellular Response to InfectionAntigenic Restimulation of Virus-Specific Memory CD8+ T Cells Requires Days of Lytic Protein Accumulation for Maximal Cytotoxic CapacityAntigen-specific CD8+ T cells play a major role in controlling most virus infections, primarily by perforin (PRF)- and granzyme B (GrB)-mediated apoptosis. There is considerable controversy regarding whether PRF is constitutively expressed, rapidly increased similarly to a cytokine, or delayed in its expression with more prolonged stimulation in virus-specific memory CD8+ T cells. In this study, the degree of...
Transformation and Oncogenesis
Transformation and OncogenesisRole of DNA Methylation and CpG Sites in the Viral Telomerase RNA Promoter during Gallid Herpesvirus 2 PathogenesisPrevious studies demonstrated that telomerase RNAs possess functions that promote tumor development independent of the telomerase complex. vTR is a herpesvirus-encoded telomerase RNA subunit that plays a crucial role in virus-induced tumorigenesis and is expressed by a robust viral promoter that is highly regulated by the c-Myc oncoprotein binding to the E-boxes. Here, we demonstrated that the DNA methylation patterns in the functional...
Vaccines and Antiviral Agents
Vaccines and Antiviral Agents | SpotlightCharacterization of Novel Cross-Reactive Influenza B Virus Hemagglutinin Head Specific Antibodies That Lack Hemagglutination Inhibition ActivityUnderstanding the immune response that older individuals mount to influenza virus vaccination and infection is critical in order to design better vaccines for this age group. Here, we show that older individuals make broadly neutralizing antibodies that have no hemagglutination-inhibiting activity and are less potent than strain-specific antibodies. These antibodies could drive viral escape from neutralization but did not result in...
Pathogenesis and Immunity
Pathogenesis and ImmunityContinued Evolution of H5Nx Avian Influenza Viruses in Bangladeshi Live Poultry Markets: Pathogenic Potential in Poultry and Mammalian ModelsHighly pathogenic avian influenza A(H5N1) viruses have circulated continuously in Bangladesh since 2007, and active surveillance has detected viral evolution driven by mutation and reassortment. Recently, three genetically distinct A(H5N1) reassortant viruses were detected in live poultry markets in Bangladesh. Currently, we cannot assign pandemic risk by only sequencing viruses; it must be conducted empirically. We found that the H5Nx...
Pathogenesis and ImmunityAn Early Microglial Response Is Needed To Efficiently Control Herpes Simplex Virus EncephalitisMicroglia appear to be one of the principal regulators of neuroinflammation in the central nervous system (CNS). An increasing number of studies have demonstrated that the activation of microglia could result in either beneficial or detrimental effects in different CNS disorders. Hence, the role of microglia during herpes simplex virus encephalitis (HSE) has not been fully characterized. Using experimental mouse models, we showed that...
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Journal of Virology® (JVI) explores the nature of viruses, reporting important new discoveries and pointing to new directions in research.
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