Spotlight
Gem
GemDNA Tumor Viruses and Their Contributions to Molecular BiologyThis summer marks the 51st anniversary of the DNA tumor virus meetings. Scientists from around the world will gather in Trieste, Italy, to report their latest results and to agree or disagree on the current concepts that define our understanding of this diverse class of viruses.
Structure and Assembly
Structure and AssemblyConservation and Divergence of the I-Domain Inserted into the Ubiquitous HK97 Coat Protein Fold in P22-Like BacteriophagesComparative studies of protein structures often provide insights into their evolution. The HK97 fold is a structural motif used to form the coat protein shells that encapsidate the genomes of many dsDNA phages and viruses. The structure and function of coat proteins based on the HK97 fold are often embellished by the incorporation of I-domains. In the present work we compare I-domains from three phages representative of highly divergent...
Structure and Assembly | SpotlightArchitect of Virus Assembly: the Portal Protein Nucleates Procapsid Assembly in Bacteriophage P22The existence of a single portal ring is essential to the formation of infectious virions in the tailed double-stranded DNA (dsDNA) phages, herpesviruses, and adenoviruses and, as such, is a viable antiviral therapeutic target. How only one portal is selectively incorporated at a unique vertex is unclear. In many dsDNA viruses and phages, the portal protein acts as an assembly nucleator. However, early work on phage P22 assembly in...
Structure and AssemblySelection and Characterization of a Reovirus Mutant with Increased ThermostabilityNonenveloped viruses rely on protein-protein interactions to shield their genomes from the environment. The capsid, or protective shell, must also disassemble during cell entry. In this work, we identified a determinant within mammalian orthoreovirus that regulates heat resistance, disassembly kinetics, and replicative fitness. Together, these findings show capsid function is balanced for optimal replication and for spread to a new host...
Structure and AssemblyStructure of Parvovirus B19 Decorated by Fabs from a Human AntibodyParvovirus B19 is a common human pathogen and a particular threat to children, pregnant women, and patients with sickle cell disease or AIDS. Currently, neutralizing antibody is the most efficient treatment for acute B19 infections. Research on the antigenic properties of B19 will guide the usage of these antibodies and facilitate vaccine development. We have determined and report here the high-resolution structure of B19 virus-like...
Structure and AssemblyInvestigating the Biological Relevance of In Vitro-Identified Putative Packaging Signals at the 5′ Terminus of Satellite Tobacco Necrosis Virus 1 Genomic RNAViruses preferentially encapsidate their own genomic RNA, sometimes as a result of the presence of clearly defined packaging signals (PSs) in their genome sequence. Recently, a novel form of short degenerate PSs has been proposed (N. Patel, E. C. Dykeman, R. H. A. Coutts, G. P. Lomonossoff, et al., Proc Natl Acad Sci U S A 112:2227–2232, 2015, https://doi.org/10.1073/pnas.1420812112...
Structure and AssemblyGenome Characterization, Prevalence, and Transmission Mode of a Novel Picornavirus Associated with the Threespine Stickleback Fish (Gasterosteus aculeatus)The threespine stickleback species complex is an important model system in ecological and evolutionary studies because of the large number of isolated divergent populations that are experimentally tractable. For similar reasons, its coevolution with the cestode parasite Schistocephalus solidus, its interaction with gut microbes, and the evolution of its immune system...
Genome Replication and Regulation of Viral Gene Expression
Genome Replication and Regulation of Viral Gene ExpressionMapping the Heterogeneity of Histone Modifications on Hepatitis B Virus DNA Using Liver Needle Biopsies Obtained from Chronically Infected PatientsHepatitis B virus (HBV) is a major global health concern, chronically infecting millions of patients and contributing to a rising burden of liver disease. The viral genome forms the basis for chronic infection and has been shown to be subject to regulation by epigenetic mechanisms, such as posttranslational modification of histone proteins. Here, we confirm and expand on previous results by adapting a high-resolution technique for...
Virus-Cell Interactions
Virus-Cell InteractionsModeling Herpes Simplex Virus 1 Infections in Human Central Nervous System Neuronal Cells Using Two- and Three-Dimensional Cultures Derived from Induced Pluripotent Stem CellsThis study employed human induced pluripotent stem cells (hiPSCs) to model acute and latent HSV-1 infections in two-dimensional (2D) and three-dimensional (3D) CNS neuronal cultures. We successfully established acute HSV-1 infections and infections showing features of latency. HSV-1 infection of the 3D organoids was able to spread from the outer surface of the organoid and was transported to the interior lamina, providing a model to...
Virus-Cell InteractionsCA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity PhenotypesThe specific mechanisms by which HIV-1 infects nondividing cells are unclear. A mutation in the HIV-1 capsid protein abolishes the ability of the virus to infect nondividing cells, serving as a tool to examine cell cycle dependence of HIV-1 infection. We have shown that two widely used HIV-1 molecular clones exhibit significantly different N57A infectivity phenotypes due to fewer than a handful of CA amino acid differences and that...
Virus-Cell InteractionsHACE1, an E3 Ubiquitin Protein Ligase, Mitigates Kaposi’s Sarcoma-Associated Herpesvirus Infection-Induced Oxidative Stress by Promoting Nrf2 ActivityROS play important roles in several cellular processes, and increased ROS cause several adverse effects. KSHV infection of endothelial cells induces ROS, which facilitate virus entry by amplifying the infection-induced host cell signaling cascade, which, in turn, induces the nuclear translocation of phospho-Nrf2 protein to regulate the expression of antioxidative genes and viral genes. The present study demonstrates that KSHV infection...
Virus-Cell Interactions | SpotlightTurnip Mosaic Virus Is a Second Example of a Virus Using Transmission Activation for Plant-to-Plant Propagation by AphidsTransmission activation, i.e., a viral response to the presence of vectors on infected hosts that regulates virus acquisition and thus transmission, is an only recently described phenomenon. It implies that viruses contribute actively to their transmission, something that has been shown before for many other pathogens but not for viruses. However, transmission activation has been described so far for only one virus, and it was unknown...
Virus-Cell Interactions | SpotlightThe IκB Kinases Restrict Human Cytomegalovirus InfectionInnate immune signaling is a critical defense against viral infection and represents a central host-virus interaction that frequently determines the outcomes of infections. NF-κB signaling is an essential component of innate immunity that is extensively modulated by HCMV, a significant cause of morbidity in neonates and immunosuppressed individuals. However, the roles that various facets of NF-κB signaling play during HCMV infection...
Virus-Cell InteractionsThe Extended C-Terminal Region of Influenza C Virus Nucleoprotein Is Important for Nuclear Import and Ribonucleoprotein ActivityAs a member of the Orthomyxoviridae family, the polymerase complex of the influenza C virus structurally resembles its influenza A and influenza B virus counterparts, but the nucleoprotein differs by possessing an extra C-terminal region. We have characterized this region in view of nuclear import and interaction with the importin α protein family. Our results demonstrate the functional significance of a previously...
Virus-Cell InteractionsA Noncanonical Function of Polycomb Repressive Complexes Promotes Human Cytomegalovirus Lytic DNA Replication and Serves as a Novel Cellular Target for Antiviral InterventionPolycomb group (PcG) proteins are primarily known as transcriptional repressors that modify chromatin and contribute to the establishment and maintenance of cell fates. Furthermore, emerging evidence indicates that overexpression of PcG proteins in various types of cancers contributes to the dysregulation of cellular proliferation. Consequently, several inhibitors targeting PcG proteins are presently undergoing preclinical and clinical...
Virus-Cell InteractionsMarek's Disease Virus Disables the ATR-Chk1 Pathway by Activating STAT3MDV is used as a biomedical model to study virus-induced lymphoma due to the similar genomic structures and physiological characteristics of MDV and human herpesviruses. Upon infection, MDV induces DNA damage, which may activate the DDR pathway. The DDR pathway has a dual impact on viruses because it manipulates repair and recombination factors to facilitate viral replication and also initiates antiviral action by regulating other...
Virus-Cell InteractionsHsp27 Responds to and Facilitates Enterovirus A71 Replication by Enhancing Viral Internal Ribosome Entry Site-Mediated TranslationOutbreaks of infections with EV-A71, which causes hand, foot, and mouth disease, severe neurological disorders, and even death, have been repeatedly reported worldwide in recent decades and are a great public health problem for which no approved treatments are available. We show that Hsp27, a heat shock protein, supports EV-A71 infection in two distinct ways to promote viral IRES-dependent translation. A small-molecule Hsp27 inhibitor...
Cellular Response to Infection
Cellular Response to InfectionPersistent Replication of HIV, Hepatitis C Virus (HCV), and HBV Results in Distinct Gene Expression Profiles by Human NK CellsThree viruses exist that can result in persistently high viral loads in immunocompetent humans: human immunodeficiency virus (HIV), hepatitis C virus, and hepatitis B virus. In the last decades, by using flow cytometry and in vitro assays on NK cells from patients with these types of infections, several impairments have been established, particularly during and possibly contributing to HIV viremia. However, the background of NK...
Cellular Response to InfectionManipulation of Aphid Behavior by a Persistent Plant VirusThis study demonstrates that a persistent plant virus can manipulate aphid behavior. This manipulation is in stark contrast to previously described effects of acute viruses on their hosts that facilitate their transmission. This study demonstrates a positive relationship between Pepper cryptic virus 1 and jalapeño pepper (...
Vaccines and Antiviral Agents
Vaccines and Antiviral AgentsV1 and V2 Domains of HIV Envelope Contribute to CCR5 Antagonist ResistanceIt is believed that each CCR5 antagonist-resistant isolate will develop its own unique set of mutations, making it difficult to identify a signature mutation that can effectively predict CCR5 antagonist resistance. This may explain why we do not observe shared mutations among clinical studies. The present study examined the earliest events in the development of drug resistance with viral quasispecies that continued the use of CCR5 for...
Vaccines and Antiviral Agents | SpotlightEffect of Previous Respiratory Syncytial Virus Infection on Murine Immune Responses to F and G Protein-Containing Virus-Like ParticlesHumans may experience repeated infections caused by the same serotype of respiratory syncytial virus (RSV), in contrast to infections with most other viruses, indicating that immune memory responses to RSV are defective. However, the effects of any residual but nonprotective immunity on responses to RSV vaccines are not clear. This study demonstrates that a VLP vaccine candidate containing a stabilized prefusion F protein can robustly...
Vaccines and Antiviral AgentsComparison of the Whole-Genome Sequence of an Oka Varicella Vaccine from China with Other Oka Vaccine Strains Reveals Sites Putatively Critical for Vaccine EfficacyVaricella, also known as chickenpox, is a highly contagious disease, caused by varicella-zoster virus (VZV). Varicella is a common childhood disease that can be prevented by a live attenuated vaccine. The first available vaccine was derived from the parental Oka strain in Japan in 1974. Several live attenuated vaccines based on the Oka strain are currently available worldwide. Among the four vaccines produced in China, the vaccine...
Vaccines and Antiviral Agents | SpotlightTherapeutic Mucosal Vaccination of Herpes Simplex Virus 2-Infected Guinea Pigs with Ribonucleotide Reductase 2 (RR2) Protein Boosts Antiviral Neutralizing Antibodies and Local Tissue-Resident CD4+ and CD8+ TRM Cells Associated with Protection against Recurrent Genital HerpesRecurrent genital herpes is one of the most common sexually transmitted diseases, with a global prevalence of HSV-2 infection predicted to be over 536 million worldwide. Despite the availability of many intervention strategies, such as sexual behavior education, barrier methods, and the costly antiviral drug treatments, eliminating or at least reducing recurrent genital herpes remains a challenge. Currently, no FDA-approved therapeutic...
Pathogenesis and Immunity
Pathogenesis and ImmunityPPAR-γ in Macrophages Limits Pulmonary Inflammation and Promotes Host Recovery following Respiratory Viral InfectionRespiratory viral infections, like IAV and respiratory syncytial virus (RSV) infections, impose great challenges to public health. Alveolar macrophages (AM) are lung-resident immune cells that play important roles in protecting the host against IAV and RSV infections. However, the underlying molecular mechanisms by which AM modulate host inflammation, disease development, and tissue recovery are not very well understood. Here we...
Pathogenesis and ImmunityHIV-1 Subtype C with PYxE Insertion Has Enhanced Binding of Gag-p6 to Host Cell Protein ALIX and Increased Replication FitnessGenomic differences within HIV-1 subtypes is associated with various degrees of viral spread, disease progression, and clinical outcome. Viral budding is essential in the HIV-1 life cycle and mainly mediated through the interaction of Gag with host proteins. Two motifs within Gag-p6 mediate binding of host cell proteins and facilitate budding. HIV-1C has a natural deletion of one of these two motifs, resulting in an inability to bind to...
Pathogenesis and ImmunitySimian Immunodeficiency Virus Infects Functionally Polarized Memory CD4 T Cells Equivalently In VivoFunctional perturbations of memory CD4 T cells have been suggested to underlie important aspects of HIV disease progression. However, the mechanisms underlying these perturbations remain unclear. Using a nonhuman primate model of HIV, we show that SIV infects functionally defined populations of memory CD4 T cells equally in different anatomic sites. Thus, preferential infection by the virus is unlikely to cause functional perturbations...
Pathogenesis and ImmunityThe US11 Gene of Herpes Simplex Virus 1 Promotes Neuroinvasion and Periocular Replication following Corneal InfectionAlphaherpesviruses are ubiquitous DNA viruses and include the human pathogens herpes simplex virus 1 (HSV-1) and HSV-2 and are significant causes of ulcerative mucosal sores, infectious blindness, encephalitis, and devastating neonatal disease. Successful primary infection and persistent coexistence with host immune defenses are dependent on the ability of these viruses to counter the antiviral response. HSV-1 and HSV-2 and other...
Pathogenesis and ImmunityAdaptation of an R5 Simian-Human Immunodeficiency Virus Encoding an HIV Clade A Envelope with or without Ablation of Adaptive Host Immunity: Differential Selection of Viral MutantsIn this study, we constructed a simian-human immunodeficiency virus carrying an R5 Kenyan HIV-1 clade A env (SHIV-A). To bypass host immunity, SHIV-A was rapidly passaged in naive macaques or animals depleted of both CD8+ and B cells. Next-generation sequencing identified different mutations that resulted from optimization of viral replicative fitness either in the absence of adaptive immunity or due to pressure from...
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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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