Table of Contents
Spotlight
Gem
GemThe RNA Epitranscriptome of DNA VirusesRNA modifications have generated much interest in the virology field, as recent works have shown that many viruses harbor these marks and modify cellular marks. The most abundant mRNA modification in eukaryotic cells, N6-methyladenosine (m6A), has been examined extensively at the genome-wide scale in both cellular and viral contexts.
Structure and Assembly
Structure and AssemblyStructural and Biochemical Characterization of Endoribonuclease Nsp15 Encoded by Middle East Respiratory Syndrome CoronavirusThe lethally pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus (SARS-CoV) pose serious threats to humans. Endoribonuclease Nsp15 encoded by coronavirus plays an important role in viral infection and pathogenesis. This study determines the structure of MERS-CoV Nsp15 and demonstrates how the catalytic activity of this protein is potentially mediated, thereby providing...
Structure and Assembly | SpotlightRole of Capsid Anchor in the Morphogenesis of Zika VirusThe capsid anchor (Ca) is a single-pass transmembrane domain at the C terminus of the capsid protein (C) known to function as a signal for the translocation of PrM into the ER lumen. The objective of this study was to further examine the role of Ca in Zika virus life cycle, whether involved in the formation of nucleocapsid through association with C or in the formation of viral envelope. In this study, we show that Ca has a function...
Structure and AssemblyQualitative Differences in Capsidless L-Particles Released as a By-Product of Bovine Herpesvirus 1 and Herpes Simplex Virus 1 InfectionsThe alphaherpesvirus family includes viruses that infect humans and animals. Hence, not only do they have a significant impact on human health, but they also have a substantial economic impact on the farming industry. While the pathogenic manifestations of the individual viruses differ from host to host, their relative genetic compositions suggest similarity at the molecular level. This study provides a side-by-side comparison of the...
Structure and AssemblyInfluenza A Virus M2 Protein Apical Targeting Is Required for Efficient Virus ReplicationInfluenza A virus assembly and particle release occur at the apical membrane of polarized epithelial cells. The integral membrane proteins encoded by the virus, HA, NA, and M2, are all targeted to the apical membrane and believed to recruit the other structural proteins to sites of virus assembly. By targeting M2 to the basolateral or endoplasmic reticulum membranes, influenza A virus replication was significantly reduced. Basolateral...
Genome Replication and Regulation of Viral Gene Expression
Genome Replication and Regulation of Viral Gene ExpressionKaposi's Sarcoma-Associated Herpesvirus Deregulates Host Cellular Replication during Lytic Reactivation by Disrupting the MCM Complex through ORF59KSHV is the causative agent of various lethal malignancies affecting immunocompromised individuals. Both lytic and latent phases of the viral life cycle contribute to the progression of these cancers. A better understanding of how viral proteins disrupt functions of a normal healthy cell to cause oncogenesis is warranted. One crucial lytic protein produced early during lytic reactivation is the multifunctional ORF59. In this report, we...
Genome Replication and Regulation of Viral Gene ExpressionThe Human Bocavirus 1 NP1 Protein Is a Multifunctional Regulator of Viral RNA ProcessingThe Parvovirinae are small nonenveloped icosahedral viruses that are important pathogens in many animal species, including humans. The NP1 protein of human bocavirus 1 (HBoV1), similar to NP1 of the bocavirus minute virus of canine (MVC), regulates viral alternative RNA processing by both suppressing polyadenylation at an internal site, (pA)p, and facilitating...
Genome Replication and Regulation of Viral Gene ExpressionComplementary Mutations in the N and L Proteins for Restoration of Viral RNA SynthesisDuring viral RNA synthesis of a negative-strand RNA virus, the viral RNA-dependent RNA polymerase (vRdRp) must gain access to the sequestered RNA in the nucleocapsid to use it as the template, but at the same time may not disrupt the nucleocapsid assembly. Our structural and mutagenesis studies showed that a flexible structural motif acts as a potential access gate to the sequestered RNA and plays an essential role in viral RNA...
Genetic Diversity and Evolution
Genetic Diversity and EvolutionPolymorphisms in Rhesus Macaque Tetherin Are Associated with Differences in Acute Viremia in Simian Immunodeficiency Virus Δnef-Infected AnimalsAs a consequence of ongoing evolutionary conflict with viral pathogens, tetherin has accumulated numerous species-specific differences that represent important barriers to the transmission of viruses between species. This study reveals extensive polymorphism in rhesus macaque tetherin and identifies specific alleles that are associated with lower viral loads during the first few weeks after infection with nef-deleted SIV. These...
Genetic Diversity and EvolutionLarge-Scale Synonymous Substitutions in Cucumber Mosaic Virus RNA 3 Facilitate Amino Acid Mutations in the Coat ProteinRecently, it has been known that synonymous substitutions in RNA virus genes affect viral pathogenicity and competitive fitness by alteration of global or local RNA secondary structure of the viral genome. We confirmed that large-scale synonymous substitutions in the CP gene of CMV resulted in decreased viral RNA titer. Importantly, when viral evolution was stimulated by serial-passage inoculation, viral RNA titer was rapidly restored,...
Genetic Diversity and EvolutionSequence Variation of Epstein-Barr Virus: Viral Types, Geography, Codon Usage, and DiseasesEpstein-Barr virus causes most cases of infectious mononucleosis and posttransplant lymphoproliferative disease. It contributes to several types of cancer, including Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. EBV genome variation is important because some of the diseases associated with EBV have very different incidences in different populations and geographic...
Virus-Cell Interactions
Virus-Cell InteractionsLocalization and Regulation of the T1 Unimolecular SpaninSpanins have been proposed to fuse the cytoplasmic and outer membranes during phage lysis. Recent work with the lambda spanins Rz-Rz1, which are similar to class I viral fusion proteins, has shed light on the functional domains and requirements for two-component spanin function. Here we report, for the first time, a genetic and biochemical approach to characterize unimolecular spanins, which are structurally and mechanistically...
Virus-Cell InteractionsThe Coronavirus Transmissible Gastroenteritis Virus Evades the Type I Interferon Response through IRE1α-Mediated Manipulation of the MicroRNA miR-30a-5p/SOCS1/3 AxisType I interferons (IFN-I) play essential roles in restricting viral infections. Coronavirus infection induces ER stress and the interferon response, which reflects different adaptive cellular processes. An understanding of how coronavirus-elicited ER stress is actively involved in viral replication and manipulates the host IFN-I response has remained elusive. Here, TGEV inhibited host miR-30a-5p via the ER stress sensor IRE1α, which...
Virus-Cell InteractionsAn N-Glycosylated Form of SERINC5 Is Specifically Incorporated into HIV-1 VirionsSERINC5 is a member of a family of multipass transmembrane proteins that inhibit the infectivity of retroviruses, including HIV-1. These proteins are incorporated into virions and inhibit infection of target cells unless counteracted by viral antagonists such as HIV-1 Nef. The only other biological function with which these proteins have been associated is the formation of serine-containing membrane lipids. Here we show that SERINC5 is...
Virus-Cell Interactions | SpotlightPJA1 Coordinates with the SMC5/6 Complex To Restrict DNA Viruses and Episomal Genes in an Interferon-Independent MannerDNA viruses, including hepatitis B virus and herpes simplex virus, induce a series of immune responses in the host and lead to human public health concerns worldwide. In addition to cytokines in the cytoplasm, restriction of viral DNA in the nucleus is an important approach of host immunity. However, the mechanism of foreign DNA recognition and restriction in the cell nucleus is largely unknown. This work demonstrates that an important...
Virus-Cell InteractionsHuman Immunodeficiency Virus Type 1 gp120 and Tat Induce Mitochondrial Fragmentation and Incomplete Mitophagy in Human NeuronsDespite viral suppression by antiretrovirals, HIV proteins continue to be detected in infected cells and neurologic complications remain common in infected people. Although HIV is unable to infect neurons, viral proteins, including gp120 and Tat, can enter neurons and can cause neuronal degeneration and neurocognitive impairment. Neuronal health is dependent on the functional integrity of mitochondria, and damaged mitochondria are...
Cellular Response to Infection
Cellular Response to InfectionExchange Proteins Directly Activated by cAMP and Their Roles in Respiratory Syncytial Virus InfectionRSV is a serious public health problem, as it is associated with bronchiolitis, pneumonia, and asthma exacerbations. Currently no effective treatment or vaccine is available, and many molecular mechanisms regarding RSV-induced lung disease are still significantly unknown. This project aims to elucidate an important and novel function of a protein, called EPAC2, in RSV replication and innate inflammatory responses. Our results should...
Vaccines and Antiviral Agents
Vaccines and Antiviral Agents | SpotlightDevelopment of a Pan-H1 Influenza VaccineSeasonal influenza vaccines elicit strain-specific immune responses designed to protect against circulating viruses. Because these vaccines often show limited efficacy, the search for a broadly protective seasonal vaccine remains a priority. Among different influenza virus subtypes, H1N1 has long been circulating in humans and has caused pandemic outbreaks. In order to assess the potential of a multivalent HA combination vaccine to...
Pathogenesis and Immunity
Pathogenesis and ImmunityAcidity/Alkalinity of Japanese Encephalitis Virus E Protein Residue 138 Alters Neurovirulence in MiceThe E protein is the only glycoprotein in mature JEV, and it plays an important role in viral neurovirulence. E protein mutations attenuate JEV neurovirulence through unclear mechanisms. Here, we discovered that E138 is a predominant determinant of JEV neurovirulence. We demonstrated that the alkalinity/acidity of E138 determines JEV neurovirulence. These data contribute to the characterization of the E protein and the rational...
Pathogenesis and Immunity | SpotlightInhibition of MALT1 Decreases Neuroinflammation and Pathogenicity of Virulent Rabies Virus in MiceRabies virus is a neurotropic RNA virus that causes encephalitis and still poses an enormous challenge to animal and public health. Efforts to establish reliable therapeutic strategies have been unsuccessful and are hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular protease that mediates the activation of several innate and adaptive immune cells in response to multiple receptors, and therapeutic...
Pathogenesis and ImmunityAntibody-Mediated CD4 Depletion Induces Homeostatic CD4+ T Cell Proliferation without Detectable Virus Reactivation in Antiretroviral Therapy-Treated Simian Immunodeficiency Virus-Infected MacaquesDespite successful suppression of HIV replication with antiretroviral therapy, current treatments are unable to eradicate the latent virus reservoir, and treatment interruption almost invariably results in the reactivation of HIV even after decades of virus suppression. Homeostatic proliferation of latently infected cells is one mechanism that could maintain the latent reservoir. To understand the impact of homeostatic mechanisms on...
Pathogenesis and ImmunityComparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A VirusesDue to the rapid evolution of the influenza A virus, vaccines require continuous strain updates. Additionally, the platform used to deliver the vaccine can have an impact on the breadth of protection. Currently, there are various vaccine platforms available to prevent influenza A virus infection in swine, and we experimentally tested two: adjuvanted-whole inactivated virus and live-attenuated virus. When challenged with an antigenically...
Pathogenesis and ImmunityComparative In Vitro and In Vivo Analysis of H1N1 and H1N2 Variant Influenza Viruses Isolated from Humans between 2011 and 2016Influenza A virus is a continuously evolving respiratory pathogen. Endemic in swine, H1 and H3 subtype viruses sporadically cause human infections. As each zoonotic infection represents an opportunity for human adaptation, the emergence of a transmissible influenza virus to which there is little or no preexisting immunity is an ongoing threat to public health. Recently isolated variant H1 subtype viruses were shown to display extensive...
Pathogenesis and Immunity | SpotlightHerpes Simplex Virus 1 Specifically Targets Human CD1d Antigen Presentation To Enhance Its PathogenicityHerpes simplex virus 1 (HSV-1) is among the most common human pathogens. Little is known regarding the exact mechanism by which this virus evades the human immune system, particularly the innate immune system. We reported previously that HSV-1 employs its protein kinase US3 to modulate the expression of the key antigen-presenting molecule, CD1d, so as to evade the antiviral function of NKT cells. Here we demonstrated that the virus has...
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