Editorial
Spotlight
Structure and Assembly
Structure and AssemblyCapsid Structure of Leishmania RNA Virus 1Twelve million people worldwide suffer from leishmaniasis, resulting in more than 30 thousand deaths annually. The disease has several variants that differ in their symptoms.
Structure and AssemblyThe SARS-CoV-2 Conserved Macrodomain Is a Mono-ADP-RibosylhydrolaseSARS-CoV-2 has recently emerged into the human population and has led to a worldwide pandemic of COVID-19 that has caused more than 1.2 million deaths worldwide. With no currently approved treatments, novel therapeutic strategies are desperately needed.
Structure and AssemblyN-Linked Glycosylation Plays an Important Role in Budding of Neuraminidase Protein and Virulence of Influenza VirusesNA is a highly glycosylated protein. Nevertheless, how the NLG affects the function of NA protein remains largely unclear.
Structure and AssemblyCharacterization of Localization and Export Signals of Bovine Torovirus Nucleocapsid Protein Responsible for Extensive Nuclear and Nucleolar Accumulation and Their Importance for Virus GrowthToVs are diarrhea-causing pathogens detected in many species, including humans. BToV has spread worldwide, leading to economic loss, and there is currently no treatment or vaccine available.
Genome Replication and Regulation of Viral Gene Expression
Genome Replication and Regulation of Viral Gene ExpressioncDNA-Derived RNA Phage Assembly Reveals Critical Residues in the Maturation Protein of the Pseudomonas aeruginosa Leviphage PP7The biological significance of RNA phages has been largely ignored, ironically, because few studies have focused on RNA phages. As an initial attempt to properly represent RNA phages in the phageome, we previously created, by using reverse-transcribed cDNA, a reverse genetic system for the small RNA phage PP7, which infects the opportunistic human pathogen Pseudomonas...
Genome Replication and Regulation of Viral Gene ExpressionCharacterization of Hepatitis B Precore/Core-Related AntigensChronic hepatitis B virus (HBV) infection afflicts approximately 257 million people, who are at high risk of progressing to chronic liver diseases, including fibrosis, cirrhosis, and hepatocellular carcinoma. Current therapies rarely achieve cure of HBV infection due to the persistence of the HBV episome, the covalently closed circular DNA (cccDNA), in the nuclei of infected hepatocytes. Peripheral markers of cccDNA levels and...
Genetic Diversity and Evolution
Genetic Diversity and EvolutionA Founder Effect Led Early SARS-CoV-2 Transmission in SpainMultiple SARS-CoV-2 introductions have been detected in Spain, and at least four resulted in the emergence of locally transmitted clusters that originated not later than mid-February, with further dissemination to many other countries around the world, and a few weeks before the explosion of COVID-19 cases detected in Spain during the first week of March. The majority of the earliest variants detected in Spain branched in the clade 19B...
Genetic Diversity and EvolutionVirome of Bat Guano from Nine Northern California RoostsCharacterizing the bat virome is important for understanding viral diversity and detecting viral spillover between animal species. Using an unbiased metagenomics method, we characterize the virome in guano collected from multiple roosts of common Northern California bat species. We describe several novel viral genomes and report the detection of viruses with close relatives reported in other bat species, likely reflecting cross-species...
Genetic Diversity and EvolutionUnexpected Discovery and Expression of Amphibian Class II Endogenous RetrovirusesClass II retroviruses, largely distributed among mammals and birds, are of particular importance for medicine and economics. Class II ERVs have been discovered in a range of vertebrates, with the exception of amphibians, which are known only to possess class I and class III-like ERVs.
Virus-Cell Interactions
Virus-Cell InteractionsThe Inflammasome Components NLRP3 and ASC Act in Concert with IRGM To Rearrange the Golgi Apparatus during Hepatitis C Virus InfectionNumerous pathogens can affect cellular homeostasis and organelle dynamics. Hepatitis C virus (HCV) triggers Golgi fragmentation through the immunity-related GTPase M (IRGM), a resident Golgi protein, to enhance its lipid supply for replication.
Virus-Cell InteractionsDual Pathways of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trafficking Modulate the Selective Exclusion of Uncleaved Oligomers from VirionsThe envelope glycoprotein (Env) trimers on the surface of human immunodeficiency virus type 1 (HIV-1) mediate the entry of the virus into host cells and serve as targets for neutralizing antibodies. The cleaved, functional Env is incorporated into virus particles from the surface of the infected cell. We found that an uncleaved form of Env is transported to the cell surface by an unconventional route, but this nonfunctional Env is...
Virus-Cell InteractionsProhibitin-1 Contributes to Cell-to-Cell Transmission of Herpes Simplex Virus 1 via the MAPK/ERK Signaling PathwayHerpesviruses are ubiquitous pathogens of various animals, including humans. These viruses primarily pass through cell junctions to spread to uninfected cells.
Virus-Cell InteractionsHuman Noroviruses Attach to Intestinal Tissues of a Broad Range of Animal SpeciesNoroviruses are a major cause of acute gastroenteritis in humans. New norovirus variants and recombinants (re)emerge regularly in the human population. From animal experiments and surveillance studies, it has become clear that at least seven animal models are susceptible to infection with human strains and that domesticated and wild animals shed human noroviruses in their feces. As virus attachment is an important first step for...
Virus-Cell InteractionsHuman Cytomegalovirus Interactions with the Basement Membrane Protein Nidogen 1We have found that HCMV infection promotes the elimination of the developmentally important basement membrane protein nidogen 1 (NID1) from its host. The virus both decreased transcription and induced degradation of expressed protein.
Virus-Cell Interactions | SpotlightCD300lf Conditional Knockout Mouse Reveals Strain-Specific Cellular Tropism of Murine NorovirusHuman noroviruses (HuNoVs) are a leading cause of gastroenteritis resulting in up to 200,000 deaths each year. The receptor and cell tropism of HuNoV in immunocompetent humans are unclear.
Virus-Cell InteractionsEnterovirus D68 Protease 2Apro Targets TRAF3 To Subvert Host Innate Immune ResponsesHuman enterovirus 68 (EV-D68) has received considerable attention recently as a global reemergent pathogen because it causes severe respiratory tract infections and acute flaccid myelitis. The nonstructural protein 2A protease (2Apro) of EV, which functions in cleavage of host proteins, comprises an essential part of the viral immune evasion process. However, the pathogenic mechanism of EV-D68 is not fully understood. Here,...
Virus-Cell Interactions | SpotlightChikungunya Virus Replication Rate Determines the Capacity of Crossing Tissue Barriers in MosquitoesIt is well established that selective pressures in mosquito vectors impose population bottlenecks for arboviruses. Here, we used a CHIKV Caribbean lineage mutant carrying a deletion in the 3′ UTR to study host-virus interactions in vivo in the epidemic mosquito vector Aedes aegypti. We found that the mutant virus had a delayed replication rate in mosquitoes,...
Virus-Cell InteractionsTRAF6 and TAK1 Contribute to SAMHD1-Mediated Negative Regulation of NF-κB SignalingCells respond to pathogen infection by activating a complex innate immune signaling pathway, which culminates in the activation of transcription factors and secretion of a family of functionally and genetically related cytokines. However, excessive immune activation may cause tissue damage and detrimental effects on the host.
Virus-Cell InteractionsHuman Papillomavirus 16 L2 Recruits both Retromer and Retriever Complexes during Retrograde Trafficking of the Viral Genome to the Cell NucleusPrevious studies identified sorting nexins 17 and 27, as well as the retromer complex, as playing a role in HPV infection. This study shows that the newly identified retriever complex also plays an important role and begins to shed light on how both sorting nexins contribute to retromer and retriever recruitment during the infection process.
Virus-Cell InteractionsCD34+ Hematopoietic Progenitor Cell Subsets Exhibit Differential Ability To Maintain Human Cytomegalovirus Latency and Persistence...Human cytomegalovirus infection is associated with severe disease in transplant patients, and understanding how latency and reactivation occur in stem cell populations is essential to understand disease. CD34+ hematopoietic progenitor cells (HPCs) are a critical viral reservoir; however, these cells are a heterogeneous pool with donor-to-donor variation in functional, genetic, and phenotypic characteristics.
Virus-Cell InteractionsThe Vaccinia Virus B12 Pseudokinase Represses Viral Replication via Interaction with the Cellular Kinase VRK1 and Activation of the Antiviral Effector BAFViruses from diverse families encode both positive and negative regulators of viral replication. While their functions can sometimes be enigmatic, investigation of virus-encoded, negative regulators of viral replication has revealed fascinating aspects of virology.
Cellular Response to Infection
Cellular Response to InfectionNovel Oncolytic Herpes Simplex Virus 1 VC2 Promotes Long-Lasting, Systemic Anti-melanoma Tumor Immune Responses and Increased Survival in an Immunocompetent B16F10-Derived Mouse Melanoma ModelCurrent oncolytic virotherapies possess limited response rates. However, when certain patient selection criteria are used, oncolytic virotherapy response rates have been shown to increase.
Cellular Response to Infection | SpotlightDissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA LevelThe HSV-1 virion host shutoff (vhs) protein efficiently cleaves both host and viral mRNAs in a translation-dependent manner. In this study, we model and quantify changes in vhs activity, as well as virus-induced global loss of host transcriptional activity, during productive HSV-1 infection. In general, HSV-1-induced alterations in total RNA levels were dominated by these two global effects. In contrast, chromatin-...
Vaccines and Antiviral Agents
Vaccines and Antiviral Agents | SpotlightIdentification of an Antiretroviral Small Molecule That Appears To Be a Host-Targeting Inhibitor of HIV-1 AssemblyThe success of antiretroviral treatment for HIV-1 is at risk of being undermined by the growing problem of drug resistance. Thus, there is a need to identify antiretrovirals that act on viral life cycle stages not targeted by drugs in use, such as the events of HIV-1 Gag assembly. To address this gap, we developed a compound screen that recapitulates the intracellular events of HIV-1 assembly, including virus-host interactions that...
Vaccines and Antiviral AgentsA Novel Live Attenuated Respiratory Syncytial Virus Vaccine Candidate with Mutations in the L Protein SAM Binding Site and the G Protein Cleavage Site Is Protective in Cotton Rats and a Rhesus MacaqueGlobally, respiratory syncytial virus (RSV) is a major cause of death in children under 1 year of age, yet no vaccine is available. We have generated a novel RSV live attenuated vaccine candidate containing mutations in the L and G proteins.
Vaccines and Antiviral AgentsSystematic Assessment of Antiviral Potency, Breadth, and Synergy of Triple Broadly Neutralizing Antibody Combinations against Simian-Human Immunodeficiency VirusesOptimal bNAb immunotherapeutics will need to mediate multiple antiviral functions against a broad range of HIV strains. Our systematic assessment of triple bNAb combinations against SHIVs will identify bNAbs with synergistic, polyfunctional antiviral activity that will inform the selection of candidate bNAbs for optimal combination designs. The identified combinations can be validated in vivo in future passive immunization...
Vaccines and Antiviral AgentsEffective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin DerivativesThe emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, in late 2019 and its subsequent spread to the rest of the world has created a pandemic situation unprecedented in modern history. While ACE2 has been identified as the viral receptor, cellular polysaccharides have also been implicated in virus entry.
Vaccines and Antiviral AgentsA Replication-Defective Influenza Virus Harboring H5 and H7 Hemagglutinins Provides Protection against H5N1 and H7N9 Infection in MiceAvian influenza H5N1 and H7N9 viruses infected humans with high mortality rates. A highly safe and effective vaccine is needed to protect against a potential pandemic.
Pathogenesis and Immunity
Pathogenesis and ImmunityMiddle East Respiratory Syndrome Coronavirus Gene 5 Modulates Pathogenesis in MiceMiddle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus causing human infections with high mortality rate (∼35%). Animal models together with reverse-genetics systems are essential to understand MERS-CoV pathogenesis. We developed a reverse-genetics system for a mouse-adapted MERS-CoV that reproduces the virus behavior observed in humans. This system is highly useful to investigate the role of specific viral genes in...
Pathogenesis and ImmunityMarek’s Disease Virus Requires Both Copies of the Inverted Repeat Regions for Efficient In Vivo Replication and PathogenesisMarek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that infects chickens and causes losses in the poultry industry of up to $2 billion per year. The virus is also widely used as a model to study alphaherpesvirus pathogenesis and virus-induced tumor development in a natural host. MDV and most other herpesviruses harbor direct or inverted repeats regions in their genome. However, the role of these sequence duplications in...
Pathogenesis and ImmunityDeep Gene Sequence Cluster Analyses of Multi-Virus-Infected Mucosal Tissue Reveal Enhanced Transmission of Acute HIV-1During heterosexual HIV-1 transmission, a genetic bottleneck occurs in the newly infected individual as the virus passes from the mucosa, leading to systemic infection with a single transmitted HIV-1 clone in the recipient. This bottleneck in the recipient has just been described, and the mechanisms involved in this selection process have not been elucidated.
Pathogenesis and ImmunityInfluenza Virus Neuraminidase Engages CD83 and Promotes Pulmonary InjuryThe massive release of circulating mediators of inflammation is responsible for lung injury during influenza A virus infection. This phenomenon is referred to as the “cytokine storm.” However, the mechanism by which influenza induces the cytokine storm is not fully understood.
Pathogenesis and Immunity | SpotlightChanges in SARS-CoV-2 Spike versus Nucleoprotein Antibody Responses Impact the Estimates of Infections in Population-Based Seroprevalence StudiesIn the present study, we have determined SARS-CoV-2-specific antibody responses in sera of acute and postinfection phase subjects. Our results indicate that antibody responses against viral S and N proteins were equally sensitive in the acute phase of infection, but that responses against N appear to wane in the postinfection phase where those against the S protein persist over time. The most sensitive serological assay in both acute...
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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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