Table of Contents
Spotlight
Structure and Assembly
Structure and AssemblyLoss of the Vaccinia Virus 35-Amino-Acid Hydrophobic O3 Protein Is Partially Compensated by Mutations in the Transmembrane Domains of Other Entry ProteinsEntry into cells is an essential first step in virus replication and an important target of vaccine-elicited immunity. For enveloped viruses, this step involves the fusion of viral and host membranes to form a pore allowing entry of the genome and associated proteins.
Structure and AssemblypH-Induced Conformational Changes of Human Bocavirus CapsidsHuman bocaviruses (HBoVs) are associated with disease in humans. However, the lack of an animal model and a versatile cell culture system to study their life cycle limits the ability to develop specific treatments or vaccines.
Structure and AssemblyA Putative Amphipathic Alpha Helix in Hepatitis B Virus Small Envelope Protein Plays a Critical Role in the Morphogenesis of Subviral ParticlesSVPs are the predominant viral product produced by HBV-infected hepatocytes. Their levels exceed those of virion particles by 10,000- to 100,000-fold in the blood of HBV-infected individuals.
Genome Replication and Regulation of Viral Gene Expression
Genome Replication and Regulation of Viral Gene ExpressionExpression of E8^E2 Is Required for Wart Formation by Mouse Papillomavirus 1 In VivoHPV encodes an E8^E2 protein which acts as repressors of viral gene expression and genome replication. In cultured normal keratinocytes, E8^E2 is essential for long-term episomal maintenance of HPV 31 (HPV31) genomes, but not for that of HPV16.
Genetic Diversity and Evolution
Genetic Diversity and EvolutionReovirus RNA Recombination Is Sequence Directed and Generates Internally Deleted Defective Genome Segments during PassageViruses in the Reoviridae family include important pathogens of humans and other animals and have segmented RNA genomes. Recombination in RNA virus populations can facilitate novel host exploration and increased disease severity.
Genetic Diversity and Evolution | SpotlightRapid Evolution of Enhanced Zika Virus Virulence during Direct Vertebrate Transmission ChainsWe used experimental evolution to model chains of direct and indirect Zika virus (ZIKV) transmission by serially passaging a synthetic swarm of molecularly barcoded ZIKV within and between mosquitoes and mice. We observed that direct mouse transmission chains facilitated a rapid increase in ZIKV replication and enhanced virulence in mice.
Genetic Diversity and Evolution | SpotlightA Persistent Giant Algal Virus, with a Unique Morphology, Encodes an Unprecedented Number of Genes Involved in Energy MetabolismViruses on Earth are tremendously diverse in terms of morphology, functionality, and genomic composition. Over the last decade, the conceptual gap separating viruses and cellular life has tightened because of the detection of metabolic genes in viral genomes that express complex virus phenotypes upon infection.
Virus-Cell Interactions
Virus-Cell InteractionsUsing Split Luciferase Assay and Anti-Herpes Simplex Virus Glycoprotein Monoclonal Antibodies To Predict a Functional Binding Site between gD and gH/gLVirus entry and cell-cell fusion mediated by HSV require four essential glycoproteins, gD, gH/gL, gB, and a gD receptor. Virus-neutralizing antibodies directed against any of these proteins bind to residues within key functional sites and interfere with essential steps in the fusion pathway.
Virus-Cell InteractionsAngiomotin Counteracts the Negative Regulatory Effect of Host WWOX on Viral PPxY-Mediated EgressFiloviruses (EBOV and MARV) and arenavirus (LASV) are zoonotic, emerging pathogens that cause outbreaks of severe hemorrhagic fever in humans. A fundamental understanding of the virus-host interface is critical for understanding the biology of these viruses and for developing future strategies for therapeutic intervention.
Virus-Cell InteractionsSelective Disruption of SERINC5 Antagonism by Nef Impairs Simian Immunodeficiency Virus Replication in Primary CD4+ T CellsSERINC5, a multipass transmembrane protein, is incorporated into retroviral particles during assembly. This leads to a reduction of particle infectivity by inhibiting virus fusion with the target cell membrane.
Virus-Cell InteractionsViral-Mediated Tethering to SEL1L Facilitates Endoplasmic Reticulum-Associated Degradation of IRE1Viruses infect cells of their host and force them to produce virus progeny. This can impose stress on the host cell and activate counterregulatory mechanisms.
Virus-Cell InteractionsPeste des Petits Ruminants Virus-Induced Novel MicroRNA miR-3 Contributes To Inhibit Type I IFN Production by Targeting IRAK1Peste des petits ruminants virus (PPRV) induces in the host a transient but severe immunosuppression, which threatens both small livestock and endangered susceptible wildlife populations in many countries. Despite extensive research, the mechanism underlying PPRV immune system evasion remains elusive.
Virus-Cell InteractionsLocalization of the WD Repeat-Containing Protein 5 to the Virion Assembly Compartment Facilitates Human Cytomegalovirus AssemblyHuman cytomegalovirus (HCMV) has a large (∼235-kb) genome that contains over 170 open reading frames (ORFs) and exploits numerous cellular factors to facilitate its replication. In the late phase of HCMV infection, cytoplasmic membranes are reorganized to establish the virion assembly compartment (vAC), which has been shown to be necessary for efficient assembly of progeny virions.
Virus-Cell InteractionsThe Avian Retroviral Receptor Tva Mediates the Uptake of Transcobalamin Bound Vitamin B12 (Cobalamin)We demonstrate that the ASLV receptor Tva participates in the physiological uptake of TC-Cbl because the viral infection suppresses the uptake of Cbl and vice versa. Our results pave the road for future studies addressing the following issues: (i) whether a virus infection can be inhibited by TC-Cbl complexes in vivo, and (ii) whether any human virus employs the human TC-Cbl receptor CD320.
Virus-Cell InteractionsThe Tetraspanin Protein CD9 Modulates Infection with Human Herpesvirus 6A and 6B in a CD46-Dependent MannerThe mechanisms of entry of HHV-6A and HHV-6B into host cells are of significance in order to develop novel drugs that may inhibit infection. To elucidate the contributions of the membrane proteins CD9 and CD46, we employed a genetic approach that eliminated these molecules from the host cell.
Virus-Cell Interactions | SpotlightThe Influenza A Virus Host Shutoff Factor PA-X Is Rapidly Turned Over in a Strain-Specific MannerThe PA-X protein from influenza A virus reduces host immune responses to infection through suppressing host gene expression, including genes encoding the antiviral response. Thus, it plays a central role in influenza A virus biology.
Virus-Cell InteractionsRespiratory Syncytial Virus Activates Rab5a To Suppress IRF1-Dependent Lambda Interferon Production, Subverting the Antiviral Defense of Airway Epithelial CellsThis study highlights the important role of Rab5a in respiratory syncytial virus (RSV) infection, such that its depletion inhibits RSV infection by stimulating the endogenous respiratory epithelial antiviral immunity and attenuates inflammation of the airway, which suggests that Rab5a is a powerful potential target for novel therapeutics against RSV infection.
Virus-Cell InteractionsStructural Domains of the Herpes Simplex Virus 1 gD Protein That Restrict Human Immunodeficiency Virus Particle InfectivityPreviously, we showed that unlike HSV-1, the presence of the gD glycoprotein in virus producer cells but not gB potently restricted HIV-1 particle infectivity. To better understand the relationship between cell surface expression, virus incorporation, and restriction of HIV-1, we analyzed a series of deletion mutants and chimeric proteins in which domains of gD and gB were swapped.
Cellular Response to Infection
Editor's Pick Cellular Response to Infection | SpotlightTh2 Cytokine Modulates Herpesvirus Reactivation in a Cell Type-Specific MannerHerpesviruses establish lifelong quiescent infections in specific cells in the body and reactivate to produce infectious virus only when precise signals induce them to do so. The signals that induce herpesvirus reactivation are often studied only in one particular cell type infected with the virus.
Cellular Response to InfectionCircular RNA circPIKfyve Acts as a Sponge of miR-21-3p To Enhance Antiviral Immunity through Regulation of MAVS in Teleost FishHere, we identified a novel circRNA, namely, circPIKfyve, that can act as a key regulator of the innate immune response in teleost fish. circPIKfyve acts as a molecular sponge by competitive adsorbing of miR-21-3p, thereby increasing the abundance of MAVS and activating the downstream NF-κB/IRF3 pathway to enhance the antiviral response. In addition, this study was the first to find that QKI protein is involved in regulating the...
Cellular Response to InfectionIn Chronic Infection, HIV Gag-Specific CD4+ T Cell Receptor Diversity Is Higher than CD8+ T Cell Receptor Diversity and Is Associated with Less HIV Quasispecies DiversityHuman T cells recognize portions of viral proteins bound to host molecules (human leukocyte antigens) on the surface of infected cells. T cells recognize these foreign proteins through their T cell receptors (TCRs), which are formed by the assortment of several available V, D, and J genes to create millions of combinations of unique TCRs.
Cellular Response to InfectionCAGE-Seq Reveals that HIV-1 Latent Infection Does Not Trigger Unique Cellular Responses in a Jurkat T Cell ModelLatent HIV-1 infection is established as early as the first viral exposure and remains the most important barrier in obtaining the cure for HIV-1 infection. Here, we used cap analysis of gene expression (CAGE) to compare the transcriptional landscape of latently infected cells with that of noninfected or productively infected cells.
Cellular Response to Infection | SpotlightSARS-CoV-2 Triggers an MDA-5-Dependent Interferon Response Which Is Unable To Control Replication in Lung Epithelial CellsMammalian cells express sensors able to detect specific features of pathogens and induce the interferon response, which is one of the first lines of defense against viruses and helps in controlling viral replication. The mechanisms and impact of SARS-CoV-2 sensing in lung epithelial cells remain to be deciphered.
Vaccines and Antiviral Agents
Vaccines and Antiviral AgentsNovel Lytic Phages Protect Cells and Mice against Pseudomonas aeruginosa InfectionNovel lytic phages isolated from various environmental settings were systematically characterized for their critical genetic traits, morphology structures, host ranges against laboratory strains and clinical multidrug-resistant (MDR) Pseudomonas aeruginosa isolates, and antibacterial capacity both in vitro and in mouse models. First, we characterized the...
Vaccines and Antiviral AgentsProminent Neutralizing Antibody Response Targeting the Ebolavirus Glycoprotein Subunit Interface Elicited by ImmunizationThe elicitation of sustained neutralizing antibody (nAb) responses against diverse ebolavirus strains remains a high priority for the vaccine field. The most clinically advanced rVSV-ZEBOV vaccine could elicit moderate nAb responses against only one ebolavirus strain, Zaire Ebola (EBOV), among the five ebolavirus strains, which last less than 6 months.
Vaccines and Antiviral AgentsComparison of Subgenomic and Total RNA in SARS-CoV-2-Challenged Rhesus MacaquesDeveloping therapeutic and prophylactic countermeasures for the SARS-CoV-2 virus is a public health priority. During challenge studies, respiratory viruses are delivered and sampled from the same anatomical location.
Vaccines and Antiviral AgentsEvaluating a New Class of AKT/mTOR Activators for HIV Latency-Reversing Activity Ex Vivo and In Vivo...If combined with immune therapeutics, latency-reversing agents (LRAs) have the potential to reduce the size of the reservoir sufficiently that an engineered immune response can control the virus in the absence of antiretroviral therapy. We have identified a new class of LRAs that do not induce T-cell activation and that are able to potentiate, rather than inhibit, CD8+ T and NK cell cytotoxic effector functions.
Vaccines and Antiviral AgentsScreening of Botanical Drugs against Lassa Virus EntryCurrently, there is no approved therapy to treat Lassa fever (LASF). Our goal was to identify potential candidate molecules for LASF therapy. Herein, we screened a botanical drug library and identified two compounds, casticin and bergamottin, that inhibited LASV entry via different mechanisms.
Pathogenesis and Immunity
Pathogenesis and ImmunityCD8 Lymphocyte Depletion Enhances the Latency Reversal Activity of the SMAC Mimetic AZD5582 in ART-Suppressed Simian Immunodeficiency Virus-Infected Rhesus Macaques...A favored approach to curing HIV infection aims at inducing viral expression using latency-reversing agents (LRAs) to allow the elimination of infected cells. Here, we tested a combination of two recently identified LRAs, the SMAC mimetic/IAP inhibitor AZD5582, which activates the noncanonical NF-κB pathway, and the antibody (Ab) MT807R1, which depletes CD8α+ cells, in SIV-infected rhesus macaques (RMs) on ART.
Pathogenesis and ImmunityZika Virus Infection Induced Apoptosis by Modulating the Recruitment and Activation of Proapoptotic Protein BaxSince the large outbreaks that occurred in the Pacific Islands and Latin America in 2013, Zika virus has been confirmed a neuroteratogenic pathogen and causative agent of microcephaly and other developmental anomalies of the central nervous system in children born to infected mothers. As apoptosis is widespread throughout the whole brain, studies in animal models have reinforced the link between microcephaly caused by ZIKV infection and...
Pathogenesis and ImmunityContact-Dependent Transmission of Langat and Tick-Borne Encephalitis Virus in Type I Interferon Receptor 1-Deficient MiceTick-borne encephalitis is a severe disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). Every year, between 10,000 and 12,000 people become infected with this flavivirus.
Pathogenesis and ImmunityProduction of HIV-1 Env-Specific Antibodies Mediating Innate Immune Functions Depends on Cognate Interleukin-21- Secreting CD4+ T CellsTo develop a vaccine or immunotherapy that would cure the HIV-1 infection, it is important to identify helper T cells able to mount an efficient antibody response. Here, we demonstrate that the generation of HIV-1 Env-specific antibodies facilitating antibody-dependent innate immune responses likely depends on Env-specific IL-21-secreting CD4+ T and peripheral T follicular helper cells.
Letter to the Editor
Letter to the EditorThe Enigmatic Capsid Protein of an Encephalitic Rubivirus
Masthead
Commentary
The composition and dynamics of viral mutant spectra in infected individuals advise that to avoid selection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) escape mutants, vaccination campaigns for coronavirus disease 2019 (COVID-19) should be launched when disease incidence is low.