Spotlight
Structure and Assembly
Structure and AssemblyConformational Differences between Functional Human Immunodeficiency Virus Envelope Glycoprotein Trimers and Stabilized Soluble TrimersHIV-1 envelope glycoprotein spikes mediate the entry of the virus into host cells and are a major target for vaccine-induced antibodies. Soluble forms of the envelope glycoproteins that are stable and easily produced have been characterized extensively and are being considered as vaccines. Here, we present evidence that these stabilized soluble envelope glycoproteins differ in multiple respects from the natural HIV-1 envelope...
Structure and Assembly | SpotlightRecessive Host Range Mutants and Unsusceptible Cells That Inactivate Virions without Genome Penetration: Ecological and Technical ImplicationsTo expand host range, viruses must interact with unsusceptible host cell surfaces, which could be detrimental. As observed in this study, virions were inactivated without genome penetration. This may be advantageous to potential new hosts, culling the viral population from which an expanded host range mutant could emerge. When identified, altered host range mutations were recessive. Accordingly, isolation required populations generated...
Structure and AssemblyThe Autographa californica Multiple Nucleopolyhedrovirus ac51 Gene Is Required for Efficient Nuclear Egress of Nucleocapsids and Is Essential for In Vivo VirulenceAlphabaculoviruses are lepidopteran-specific nucleopolyhedroviruses that replicate within the nucleus; however, the anterograde transport of the nucleocapsids of these viruses, which is an obligatory step for progeny virion production, is not well understood. In the present study, a unique Alphabaculovirus gene with unknown function, namely, the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac51 gene,...
Genome Replication and Regulation of Viral Gene Expression
Genome Replication and Regulation of Viral Gene ExpressionRNA Sequencing of the In Vivo Human Herpesvirus 6B Transcriptome To Identify Targets for Clinical Assays Distinguishing between Latent and Active InfectionsHuman herpesvirus 6B (HHV-6B) is a DNA virus that infects most children within the first few years of life. After primary infection, HHV-6B persists as a chronic, latent infection in many cell types. Additionally, HHV-6B can integrate into germ line chromosomes, resulting in individuals with viral DNA in every nucleated cell. Given that PCR to detect viral DNA is the mainstay for diagnosing HHV-6B infection, the characteristics of HHV-...
Genetic Diversity and Evolution
Genetic Diversity and Evolution | SpotlightCrustacean Genome Exploration Reveals the Evolutionary Origin of White Spot Syndrome VirusWSSV is the deadliest viral pathogen threatening global shrimp aquaculture. The evolutionary history of WSSV has remained a mystery, because few WSSV relatives, or nimaviruses, had been reported. Our aim was to trace the history of WSSV using the genomes of novel nimaviruses hidden in host genome data. We demonstrate that WSSV emerged from a diverse family of crustacean-infecting large DNA viruses. By comparing the genomes of WSSV and...
Genetic Diversity and EvolutionExtensive Diversity of RNA Viruses in Australian TicksEach year a growing number of individuals along the east coast of Australia experience debilitating disease following tick bites. As there is no evidence for the presence of the causative agent of Lyme disease, Borrelia burgdorferi sensu lato, in Australian ticks, the etiological basis of...
Genetic Diversity and EvolutionChikungunya Virus Fidelity Variants Exhibit Differential Attenuation and Population Diversity in Cell Culture and Adult MiceCHIKV is a reemerging global health threat that elicits debilitating arthritis in humans. There are currently no commercially available CHIKV vaccines. Like other RNA viruses, CHIKV has a high mutation rate and is capable of rapid intrahost diversification during an infection. In other RNA viruses, virus population diversity associates with disease progression; however, potential impacts of intrahost viral diversity on CHIKV arthritic...
Virus-Cell Interactions
Virus-Cell InteractionsThe Dietary Restriction-Like Gene drl-1, Which Encodes a Putative Serine/Threonine Kinase, Is Essential for Orsay Virus Infection in Caenorhabditis elegansThe recent discovery of Orsay virus, the only known natural virus of Caenorhabditis elegans, provides a unique opportunity to study virus-host interactions that mediate infection in a genetically tractable multicellular model organism. As viruses remain a global threat to human health, better insights into cellular components that enable virus infection and...
Virus-Cell InteractionsInduction and Suppression of NF-κB Signalling by a DNA Virus of DrosophilaCoevolution of multicellular organisms and their natural viruses may lead to an intricate relationship in which host survival requires effective immunity and virus survival depends on evasion of such responses. Insect antiviral immunity and reciprocal virus immunosuppression tactics have been well studied in Drosophila melanogaster, primarily during RNA, but not DNA,...
Virus-Cell Interactions | SpotlightThe Plant Noncanonical Antiviral Resistance Protein JAX1 Inhibits Potexviral Replication by Targeting the Viral RNA-Dependent RNA PolymeraseResistance genes play a crucial role in plant antiviral innate immunity. The roles of conventional nucleotide-binding leucine-rich repeat (NLR) proteins and the associated defense pathways have long been studied. In contrast, recently discovered resistance genes that do not encode NLR proteins (non-NLR resistance genes) have not been investigated extensively. Here we report that the non-NLR resistance factor JAX1, a unique jacalin-type...
Virus-Cell InteractionsDevelopment of a Primary Human Cell Model for the Study of Human Cytomegalovirus Replication and Spread within Salivary EpitheliumHuman cytomegalovirus (HCMV) infects the majority of the world’s population, and although it typically establishes a quiescent infection with little to no disease in most individuals, the virus is responsible for a variety of devastating sequelae in immunocompromised adults and in developing fetuses. Therefore, identifying the viral properties essential for replication, spread, and horizontal transmission is an important area of medical...
Virus-Cell InteractionsFoxO1 Suppresses Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication and Controls Viral LatencyKaposi’s sarcoma-associated herpesvirus (KSHV) is associated with several cancers, including Kaposi’s sarcoma (KS). Both the KSHV latent and lytic replication phases are important for the development of KS. Identification of factors regulating the KSHV latent phase-to-lytic phase switch can provide insights into the pathogenesis of KSHV-induced malignancies. In this study, we show that the antioxidant defense factor forkhead box protein...
Virus-Cell InteractionsFatty Acid Synthase Promotes the Palmitoylation of Chikungunya Virus nsP1S-palmitoylation is an important form of lipid posttranslational modification, which affects the function of proteins by regulating their transport, stability, and localization. Previous studies have shown that FASN is critical for CHIKV replication; however, the mechanism for this function of FASN remains unknown. The key zinc finger DHHC domain-containing palmitoyltransferases involved in the palmitoylation of nsP1 are not clear. We...
Virus-Cell InteractionsCell-to-Cell Transmission Is the Main Mechanism Supporting Bovine Viral Diarrhea Virus Spread in Cell CultureBVDV causes one of the most economically important viral infections for the cattle industry. The virus is able to cross the placenta and infect the fetus, leading to the birth of persistently infected animals, which are reservoirs for the spread of BVDV. The occurrence of persistent infection has hampered the efficacy of vaccination because it requires eliciting levels of protection close to sterilizing immunity to prevent fetal...
Virus-Cell InteractionsTetherin Inhibits Nipah Virus but Not Ebola Virus Replication in Fruit Bat CellsEbola virus and Nipah virus (EBOV and NiV) can cause fatal disease in humans. In contrast, infected fruit bats do not develop symptoms but can transmit the virus to humans. Why fruit bats but not humans control infection is largely unknown. Tetherin is an antiviral host cell protein and is counteracted by the EBOV glycoprotein in human cells. Here, employing model systems, we show that tetherin of fruit bats displays higher antiviral...
Virus-Cell InteractionsInfection and Functional Modulation of Human Monocytes and Macrophages by Varicella-Zoster VirusPrimary VZV infection results in the widespread dissemination of the virus throughout the host. Viral transportation is known to be directly influenced by susceptible immune cells in the circulation. Moreover, infection of immune cells by VZV results in attenuation of the antiviral mechanisms used to control infection and limit spread. Here, we provide evidence that human monocytes, which are highly abundant in the circulation, are...
Virus-Cell InteractionsUbiquitination Is Essential for Avibirnavirus Replication by Supporting VP1 Polymerase ActivityAvibirnavirus protein VP1, the RNA-dependent RNA polymerase, is responsible for IBDV genome replication, gene expression, and assembly. However, little is known about its chemical modification relating to its polymerase activity. In this study, we revealed the molecular mechanism of ubiquitin modification of VP1 via a K63-linked ubiquitin chain during infection. Lysine (K) residue 751 at the C terminus of VP1 is the target site for...
Cellular Response to Infection
Cellular Response to InfectionCellular Zinc Finger Protein 622 Hinders Human Adenovirus Lytic Growth and Limits Binding of the Viral pVII Protein to Virus DNAHuman adenoviruses (HAdVs) are common human pathogens causing a wide range of acute infections. To counteract viral pathogenicity, cells encode a variety of antiviral proteins and noncoding RNAs to block virus growth. In this study, we show that the cellular zinc finger protein 622 (ZNF622) interacts with an essential HAdV protein known as pVII. This mutual interaction limits pVII binding to viral DNA. Further, ZNF622 has a role in HAdV...
Cellular Response to InfectionHerpes Simplex Virus 1 ICP22 Suppresses CD80 Expression by Murine Dendritic CellsHSV-1-induced eye disease is a major public health problem. Eye disease is associated closely with immune responses to the virus and is exacerbated by delayed clearance of the primary infection. The immune system relies on antigen-presenting cells of the innate immune system to activate the T cell response. We found that HSV-1 utilizes a robust and finely targeted mechanism of local immune evasion. It downregulates the expression of the...
Transformation and Oncogenesis
Transformation and OncogenesisEpstein-Barr Virus Infection of Cell Lines Derived from Diffuse Large B-Cell Lymphomas Alters MicroRNA Loading of the Ago2 ComplexDiffuse large B-cell lymphoma (DLBCL) is a highly aggressive tumor of lymphoid origin which is occasionally Epstein-Barr virus (EBV) positive. MicroRNAs are found in most multicellular organisms and even in viruses such as EBV. They regulate the synthesis of proteins by binding to their cognate mRNA. MicroRNAs are tethered to their target mRNAs by “Argonaute” proteins. Here we compared the overall miRNA content of the Ago2 complex by...
Vaccines and Antiviral Agents
Vaccines and Antiviral Agents | SpotlightElicitation of Protective Antibodies against 20 Years of Future H3N2 Cocirculating Influenza Virus Variants in Ferrets Preimmune to Historical H3N2 Influenza VirusesAfter exposure to influenza virus, the host generates neutralizing anti-hemagglutinin (anti-HA) antibodies against that specific infecting influenza strain. These antibodies can also neutralize some, but not all, cocirculating strains. The goal of next-generation influenza vaccines, such as HA head-based COBRA, is to stimulate broadly protective neutralizing antibodies against all strains circulating within a subtype, in particular...
Vaccines and Antiviral AgentsA Measles Virus-Based Vaccine Candidate Mediates Protection against Zika Virus in an Allogeneic Mouse Pregnancy ModelZika virus (ZIKV) is a mosquito-borne flavivirus that causes a variety of neurological complications, including congenital birth defects. Despite the urgent need, no ZIKV vaccine has yet been licensed. Recombinant vaccine strain-derived measles viruses (MV) constitute a promising vector platform to induce immunity against foreign pathogens by expressing antigens from additional transcription units while at the same time possessing a...
Vaccines and Antiviral AgentsReplication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVACThough the RV144 phase III clinical trial showed promise that an effective vaccine against HIV-1 is possible, a successful vaccine will require improvement over the vaccine candidate (ALVAC) used in the RV144 study. With that goal in mind, we have tested in nonhuman primates an attenuated but replication-competent vector, NYVAC-KC, in direct comparison to its parental vector, NYVAC, which is replication restricted in human cells,...
Vaccines and Antiviral AgentsPriming with a Potent HIV-1 DNA Vaccine Frames the Quality of Immune Responses prior to a Poxvirus and Protein BoostThe evaluation of HIV vaccine efficacy trials indicates that protection would most likely correlate with a polyfunctional immune response involving several effector functions from all arms of the immune system. Heterologous prime-boost regimens have been shown to elicit vigorous T cell and antibody responses in nonhuman primates that, however, qualitatively and quantitatively differ depending on the respective vector systems used. The...
Pathogenesis and Immunity
Pathogenesis and ImmunityEnterovirus A71 Infection Activates Human Immune Responses and Induces Pathological Changes in Humanized MiceDespite causing self-limited hand-food-and-mouth disease in younger children, EV-A71 is consistently associated with severe forms of neurological complications and pulmonary edema. Nevertheless, only limited vaccines and drugs have been developed over the years, which is possibly due to a lack of models that can more accurately recapitulate human specificity, since human is the only natural host for wild-type EV-A71 infection. Our...
Pathogenesis and ImmunityEndosomal Toll-Like Receptors 7 and 9 Cooperate in Detection of Murine Gammaherpesvirus 68 InfectionThe two human gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), can cause aggressive forms of cancer. These herpesviruses are strictly host specific, and therefore the homolog murine gammaherpesvirus 68 (MHV68) is a widely used model to obtain in vivo insights into the interaction between these two gammaherpesviruses and their host. Like EBV and KSHV, MHV68 establishes lifelong...
Pathogenesis and ImmunityReactivation of Simian Varicella Virus in Rhesus Macaques after CD4 T Cell DepletionReactivation of latent VZV in humans can result in serious neurological complications. VZV-specific cell-mediated immunity is critical for the maintenance of latency. Similar to VZV in humans, SVV causes varicella in monkeys, establishes latency in ganglia, and reactivates to produce shingles. Here, we show that depletion of CD4 T cells in rhesus macaques results in SVV reactivation, with virus antigens found in zoster rash and SVV DNA...
Pathogenesis and Immunity | SpotlightMurine Cytomegalovirus Glycoprotein O Promotes Epithelial Cell Infection In VivoHuman cytomegalovirus is a leading cause of congenital disease. This reflects its capacity for systemic spread. A vaccine is needed, but the best viral targets are unclear. Attention has focused on the virion membrane fusion complex. It has 2 forms, so we need to know what each contributes to host colonization. One includes the virion glycoprotein O. We used murine cytomegalovirus, which has equivalent fusion complexes, to determine the...
Pathogenesis and ImmunityInterferon Alpha Enhances NK Cell Function and the Suppressive Capacity of HIV-Specific CD8+ T CellsData suggest that HIV+ individuals unable to control infection fail to do so due to impaired cytokine production and/cytotoxic effector cell function. Consequently, the success of cure agendas such as the shock-and-kill strategy will probably depend on enhancing patient effector cell function. In this regard, NK cells are of particular interest since they complement the function of CD8+ T cells. Here, we...
Pathogenesis and ImmunityRestriction of Human Cytomegalovirus Infection by Galectin-9Human cytomegalovirus (HCMV) continues to cause serious and often life-threatening disease in those with impaired or underdeveloped immune systems. This virus is able to infect and replicate in a wide range of human cell types, which enables the virus to spread to other individuals in a number of settings. Current antiviral drugs are associated with a significant toxicity profile, and there is no vaccine; these factors highlight a need...
Pathogenesis and ImmunityTwo Families of Env Antibodies Efficiently Engage Fc-Gamma Receptors and Eliminate HIV-1-Infected CellsThe “open” CD4-bound conformation of HIV-1 envelope glycoproteins is the primary target of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies present in HIV-positive (HIV+) sera, such as anti-coreceptor binding site and anti-cluster A antibodies. Here we report that the binding of these two families of antibodies is required to engage FcγRIIIa and mediate ADCC.
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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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