Table of Contents
Spotlight
Gem
GemFlavivirus Envelope Protein Glycosylation: Impacts on Viral Infection and PathogenesisFlaviviruses encode one, two, or no N-linked glycosylation sites on their envelope proteins. Glycosylation can impact virus interactions with cell surface attachment factors and also may impact virion stability and virus replication. Envelope protein glycosylation has been identified as a virulence determinant for multiple flaviviruses, but the mechanisms by which glycosylation mediates pathogenesis remain unclear. In this Gem...
Structure and Assembly
Structure and AssemblySalt Enhances the Thermostability of Enteroviruses by Stabilizing Capsid Protein InterfacesThe genus Enterovirus encompasses important contaminants of water and food (e.g., coxsackieviruses), as well as viruses of acute public health concern (e.g., poliovirus). Depending on the properties of the surrounding matrix, enteroviruses exhibit different sensitivities to heat, which in turn influences their persistence in the environment, during food treatment, and during vaccine storage. Here, we determined the effect of...
Genetic Diversity and Evolution
Genetic Diversity and EvolutionIdentification of Reptarenaviruses, Hartmaniviruses, and a Novel Chuvirus in Captive Native Brazilian Boa Constrictors with Boid Inclusion Body DiseaseBoid inclusion body disease (BIBD), caused by reptarenavirus infection, affects captive snake populations worldwide, but the reservoir hosts of reptarenaviruses remain unknown. Here, we report the identification of novel reptarenaviruses, hartmaniviruses, and a chuvirus in captive Brazilian boas with BIBD. Three of the four snakes studied showed coinfection with all three viruses, and one of the snakes harbored three novel...
Genetic Diversity and EvolutionTransmission of Koala Retrovirus from Parent Koalas to a Joey in a Japanese ZooKoRV is unique among retroviruses in that one strain (KoRV-A) is undergoing endogenization, whereas the other main subtype (KoRV-B) and another subtype (KoRV-C) are reportedly exogenous strains. Its transmission and pathogenesis are of interest in the study of retroviruses and are crucial for any conservation strategy geared toward koala health. This study provides new evidence on the modes of KoRV transmission from parent koalas to...
Genetic Diversity and EvolutionDiscovery and Characterization of Thermoproteus Spherical Piliferous Virus 1: a Spherical Archaeal Virus Decorated with Unusual FilamentsHigh-temperature environments have proven to be an important source for the discovery of new archaeal viruses with unusual particle morphologies and gene content. Our isolation of Thermoproteus spherical piliferous virus 1 (TSPV1), with numerous filaments extending from the virion surface, expands our understanding of viral diversity and provides new insight into viral replication in high-temperature environments.
Genetic Diversity and EvolutionNovel Cell-Virus-Virophage Tripartite Infection Systems Discovered in the Freshwater Lake Dishui Lake in Shanghai, ChinaVirophages are small parasitizing viruses of large/giant viruses. To our knowledge, the few isolated virophages all parasitize giant protozoan viruses (Mimiviridae) for propagation and form a tripartite infection system with hosts, here named the cell-virus-virophage (CVv) system. However, the CVv system remains largely unknown in environmental metagenomic data sets. In this study, we systematically investigated the metagenomic...
Genetic Diversity and Evolution | SpotlightSubtype Diversity of Influenza A Virus in North American Waterfowl: a Multidecade StudyWild aquatic birds are the primary natural reservoir of influenza A viruses (IAVs) and are therefore responsible for the dispersal and maintenance of IAVs representing a broad range of antigenic and genetic diversity. The aims of IAV surveillance in waterfowl not only relate to understanding the risk of spillover risk to humans, but also to improving our understanding of basic questions related to IAV evolution and ecology. By...
Genetic Diversity and EvolutionComparative Analysis of RNA Virome Composition in Rabbits and Associated EctoparasitesEctoparasites play an important role in the transmission of many vertebrate-infecting viruses, including Zika and dengue viruses. Although it is becoming increasingly clear that invertebrate species harbor substantial virus diversity, it is unclear how many of the viruses carried by invertebrates have the potential to infect vertebrate species. We used the European rabbit (...
Virus-Cell Interactions
Virus-Cell Interactions | SpotlightDouble-Stranded-RNA-Binding Protein 2 Participates in Antiviral DefensePlants employ multiple defense mechanisms to restrict viral infections, among which RNA interference is the best understood. The activation of innate immunity often leads to both local and systemic necrotic responses, which confine the virus to the infected cells and can also provide resistance to distal, noninfected parts of the organism. Systemic necrosis, which is regarded as a special form of the local hypersensitive response,...
Virus-Cell Interactions | SpotlightUbqln4 Facilitates Endoplasmic Reticulum-to-Cytosol Escape of a Nonenveloped Virus during InfectionHow a nonenveloped virus escapes from a host membrane to promote infection remains enigmatic. In the case of the nonenveloped polyomavirus SV40, penetration of the ER membrane to reach the cytosol is a decisive virus infection step. In this study, we found a new host factor called Ubqln4 that facilitates escape of SV40 from the ER into the cytosol, thereby providing a path for the virus to enter the nucleus to cause infection.
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Virus-Cell InteractionsRemodeling of the Core Leads HIV-1 Preintegration Complex into the Nucleus of Human LymphocytesHow the reverse-transcribed genome reaches the host nucleus remains a main open question related to the infectious cycle of HIV-1. The HIV-1 core has a size of ∼100 nm, largely exceeding that of the NPC channel (∼39 nm). Thus, a rearrangement of the viral CA protein organization is required to achieve an effective nuclear translocation. The mechanism of this process remains undefined due to the lack of a technology capable of...
Virus-Cell InteractionsEpstein-Barr Virus (EBV) Tegument Protein BGLF2 Suppresses Type I Interferon Signaling To Promote EBV ReactivationType I interferons are important for controlling virus infection. We have found that the Epstein-Barr virus (EBV) BGLF2 tegument protein binds to a protein in the type I interferon signaling pathway Tyk2 and inhibits the expression of genes induced by type I interferons. Treatment of EBV-infected cells with type I interferon inhibits reactivation of the virus, while expression of EBV BGLF2 reduces the ability of type I interferon to...
Virus-Cell InteractionsCD21 (Complement Receptor 2) Is the Receptor for Epstein-Barr Virus Entry into T CellsEpstein-Barr virus (EBV) has a well-described tropism for B cells and epithelial cells. Recently, we described the ability of a second strain of EBV, EBV type 2, to infect mature peripheral T cells. Using a neutralizing antibody assay, we determined that EBV uses the viral glycoprotein gp350 and the cellular protein CD21 to gain entry into mature peripheral T cells. CRISPR-Cas9 deletion of CD21 on the Jurkat T-cell line confirmed that...
Virus-Cell Interactions | SpotlightOsteopetrosis-Associated Transmembrane Protein 1 Recruits RNA Exosome To Restrict Hepatitis B Virus ReplicationHepatitis B virus (HBV) is a human pathogen infecting the liver to cause a variety of diseases ranging from acute hepatitis to advanced liver diseases, fulminate hepatitis, liver cirrhosis, and hepatocellular carcinoma, thereby causing a major health problem worldwide. In this study, we demonstrated that Ostm1 plays an inhibitory role in HBV protein production, RNA expression, and DNA replication. However, Ostm1 has no effect on the...
Virus-Cell InteractionsAlix-Mediated Rescue of Feline Immunodeficiency Virus Budding Differs from That Observed with Human Immunodeficiency VirusFIV is a nonprimate lentivirus that infects domestic cats and causes a syndrome that is reminiscent of AIDS in humans. Based on its similarity to HIV with regard to different molecular and biochemical properties, FIV represents an attractive model for the development of strategies to prevent and/or treat HIV infection. Here, we show that the Bro1 domain of the human cellular protein Alix is sufficient to rescue the budding of FIV...
Virus-Cell InteractionsEpidermal Growth Factor Receptor and Abl2 Kinase Regulate Distinct Steps of Human Papillomavirus 16 EndocytosisHuman papillomaviruses are small, nonenveloped DNA viruses that infect skin and mucosa. The so-called high-risk HPVs (e.g., HPV16, HPV18, HPV31) have transforming potential and are associated with various anogenital and oropharyngeal tumors. These viruses enter host cells by a novel endocytic pathway with unknown cellular function. To date, it is unclear how endocytic vesicle formation occurs mechanistically. Here, we addressed the role...
Gene Delivery
Gene DeliveryImpact of Natural or Synthetic Singletons in the Capsid of Human Bocavirus 1 on Particle Infectivity and ImmunoreactivityThe family of Parvoviridae comprises a wide variety of members that exhibit a unique biology and that are concurrently highly interesting as a scaffold for the development of human gene therapy vectors. A most notable example is human bocavirus 1 (HBoV1), which we and others have recently harnessed to cross-package and deliver recombinant genomes derived from another parvovirus, the adeno-associated virus (AAV). Here, we...
Vaccines and Antiviral Agents
Vaccines and Antiviral AgentsEpigenetic Suppression of HIV in Myeloid Cells by the BRD4-Selective Small Molecule Modulator ZL0580Brain-resident microglia and perivascular macrophages are important HIV reservoirs in the CNS. Persistent viral replication and latent HIV reactivation in the CNS, even under ART, are believed to occur, causing neuroinflammation and neurological disorders in HIV-infected patients. It is critical to identify new approaches that can control residual HIV replication and/or latent HIV reactivation in these reservoirs. We here report that...
Vaccines and Antiviral Agents | SpotlightTrivalent Glycoprotein Subunit Vaccine Prevents Neonatal Herpes Simplex Virus Mortality and MorbidityHerpes simplex virus is among the most serious infections of newborns. Current antiviral therapies can prevent mortality if infection is recognized early and treated promptly. Most children who survive nHSV develop lifelong neurological and behavioral deficits, despite aggressive antiviral treatment. We propose that maternal immunization could provide protection against HSV for both mother and baby. To this end, we used a trivalent...
Pathogenesis and Immunity
Pathogenesis and ImmunityMaternal Zika Virus (ZIKV) Infection following Vaginal Inoculation with ZIKV-Infected Semen in Timed-Pregnant Olive BaboonsZika virus remains a worldwide health threat, with outbreaks still occurring in the Americas. While mosquitos are the primary vector for the spread of the virus, sexual transmission of Zika virus is also a significant means of infection, especially in terms of passage from an infected to an uninfected partner. While sexual transmission has been documented in humans, and male-to-female transmission has been reported in mice, ours is the...
Pathogenesis and ImmunityCoronavirus Endoribonuclease and Deubiquitinating Interferon Antagonists Differentially Modulate the Host Response during Replication in MacrophagesMacrophages are an important cell type during coronavirus infections because they “notice” the infection and respond by inducing type I interferons, which limits virus replication. In turn, coronaviruses encode proteins that mitigate the cell’s ability to signal an interferon response. Here, we evaluated the host macrophage response to two independent mutant coronaviruses, one with reduced deubiquitinating activity (DUBmut) and the...
Pathogenesis and ImmunityEarly Transcriptional Changes within Liver, Adrenal Gland, and Lymphoid Tissues Significantly Contribute to Ebola Virus Pathogenesis in Cynomolgus MacaquesEbola virus (EBOV) remains a high-priority pathogen since it continues to cause outbreaks with high case fatality rates. Although it is well established that EBOV results in severe organ damage, our understanding of tissue injury in the liver, adrenal glands, and lymphoid tissues remains limited. We begin to address this knowledge gap by conducting longitudinal gene expression studies in these tissues, which were collected from EBOV-...
Pathogenesis and ImmunityOutbreak Severity of Highly Pathogenic Avian Influenza A(H5N8) Viruses Is Inversely Correlated to Polymerase Complex Activity and Interferon InductionCompared to the 2014-15 outbreak, the 2016-17 outbreak of influenza A(H5N8) viruses in the Netherlands and Europe was more virulent; the number of dead or diseased wild birds found and the severity of pathological changes were higher during the 2016-17 outbreak. The polymerase complex plays an important role in influenza virus virulence, and the gene segments of influenza A(H5N8) viruses reassorted extensively between the outbreaks. In...
Pathogenesis and ImmunityStructure-Guided Mutagenesis Alters Deubiquitinating Activity and Attenuates Pathogenesis of a Murine CoronavirusCoronaviruses employ a genetic economy by encoding multifunctional proteins that function in viral replication and also modify the host environment to disarm the innate immune response. The coronavirus papain-like protease 2 (PLP2) domain possesses protease activity, which cleaves the viral replicase polyprotein, and also DUB activity (deconjugating ubiquitin/ubiquitin-like molecules from modified substrates) using identical catalytic...
Pathogenesis and ImmunityAn R195K Mutation in the PA-X Protein Increases the Virulence and Transmission of Influenza A Virus in Mammalian HostsFour influenza pandemics in humans (the Spanish flu of 1918 [H1N1], the Asian flu of 1957 [H2N2], the Hong Kong flu of 1968 [H3N2], and the swine origin flu of 2009 [H1N1]) are all proposed to have been caused by avian or swine influenza viruses that acquired virulence factors through adaptive mutation or reassortment with circulating human viruses. Currently, influenza viruses circulating in animals are repeatedly transmitted to humans...
Pathogenesis and ImmunityGp37 Regulates the Pathogenesis of Avian Leukosis Virus Subgroup J via Its C TerminusALV-J can cause severe immunosuppression and myeloid leukemia in infected chickens. However, no vaccine or antiviral drug is available against ALV-J, and the mechanism for ALV-J pathogenesis needs to be elucidated. It is generally believed that gp85 and LTR of ALV contribute to its pathogenesis. Here, we found that the C terminus and the tyrosine motifs (YxxM, ITIM, and ITAM-like) in the CTD of Gp37 of ALV-J could...
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