viral entry
Virus-Cell InteractionsInvasion of Herpes Simplex Virus 1 into Murine Dermis: Role of Nectin-1 and Herpesvirus Entry Mediator as Cellular Receptors during AgingHSV-1 is a prevalent human pathogen which invades skin and mucocutaneous linings. So far, the underlying mechanisms of how the virus invades tissue, reaches its receptors, and initiates infection are still unresolved. To unravel the mechanical prerequisites that limit or favor viral invasion into tissue, we need to understand the contribution of the receptors that are involved in viral internalization. Here, we investigated the invasion...
GemBreaking the Convention: Sialoglycan Variants, Coreceptors, and Alternative Receptors for Influenza A Virus EntryThe influenza A virus (IAV) envelope protein hemagglutinin binds α2,6- or α2,3-linked sialic acid as a host cell receptor. Bat IAV subtypes H17N10 and H18N11 form an exception to this rule and do not bind sialic acid but enter cells via major histocompatibility complex (MHC) class II.
Virus-Cell InteractionsIntegrin β1 Promotes Peripheral Entry by Rabies VirusRabies is a severe zoonotic disease caused by rabies virus (RABV). However, the nature of RABV entry remains unclear, which has hindered the development of therapy for rabies. It is suggested that modulations of RABV glycoprotein and multiple host factors are responsible for RABV invasion. Here, we showed that integrin β1 (ITGB1) directly interacts with RABV glycoprotein, and both proteins are internalized together into host cells....
Virus-Cell InteractionsTransmembrane Domain Dissociation Is Required for Hendra Virus F Protein Fusogenic ActivityThe paramyxovirus Hendra virus (HeV) causes severe respiratory illness and encephalitis in humans. To develop therapeutics for HeV and related viral infections, further studies are needed to understand the mechanisms underlying paramyxovirus fusion events. Knowledge gained in studies of the HeV fusion (F) protein may be applicable to a broad span of enveloped viruses. In this study, we demonstrate that disulfide bonds introduced between...
Virus-Cell InteractionsKaposi Sarcoma-Associated Herpesvirus Glycoprotein H Is Indispensable for Infection of Epithelial, Endothelial, and Fibroblast Cell TypesAll homologues of herpesvirus gH studied to date have been implicated in playing an essential role in viral infection of diverse permissive cell types. However, the role of gH in the mechanism of KSHV infection remains largely unresolved. In this study, we generated a gH-null mutant KSHV and provided evidence that deficiency of gH expression did not affect viral particle assembly or egress. Using the gH-null mutant, we showed that gH...
Virus-Cell Interactions | SpotlightIdentification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular MimicryThe most recent Ebola virus disease outbreak, from 2014 to 2016, resulted in approximately 28,000 individuals becoming infected, which led to over 12,000 causalities worldwide. The particularly high pathogenicity of the virus makes paramount the identification and development of promising lead compounds to serve as inhibitors of Ebola infection. To limit viral load, the virus-host membrane fusion event can be targeted through the...
Vaccines and Antiviral AgentseCD4-Ig Limits HIV-1 Escape More Effectively than CD4-Ig or a Broadly Neutralizing AntibodyHIV-1 broadly neutralizing antibodies (bNAbs) and engineered antibody-like inhibitors have been compared for their breadths, potencies, and in vivo half-lives. However, a key limitation in the use of antibodies to treat an established HIV-1 infection is the rapid emergence of fully resistant viruses. Entry inhibitors of similar breadths and potencies can differ in the ease with which viral escape variants arise. Here we show...
Virus-Cell InteractionsIdentification of Clotrimazole Derivatives as Specific Inhibitors of Arenavirus FusionEmerging human-pathogenic arenaviruses are causative agents of severe hemorrhagic fevers with high mortality and represent serious public health problems. The current lack of a licensed vaccine and the limited treatment options makes the development of novel antiarenaviral therapeutics an urgent need. Using a recombinant pseudotype platform, we uncovered that clotrimazole drugs, in particular TRAM-34, specifically inhibit cell entry of...
Virus-Cell InteractionsRole of Sphingomyelin in Alphaherpesvirus EntryBovine herpesvirus 1 (BoHV-1) is an ubiquitous pathogen affecting cattle populations worldwide. Infection can result in complicated, polymicrobial infections due to the immunosuppressive properties of the virus. Available vaccines limit disease severity and spread but do not prevent infection. The financial and animal welfare ramifications of BoHV-1 are significant. In order to develop more effective prevention and treatment regimens, a...
Virus-Cell InteractionsLow-pH Endocytic Entry of the Porcine Alphaherpesvirus Pseudorabies VirusPRV is a pathogen of great economic and animal welfare importance in many parts of the world. PRV causes neurological, respiratory, and reproductive disorders, often resulting in mortality of young and immunocompromised animals. Mortality, decreased production, and trade restrictions result in significant financial losses for the agricultural industry. Understanding the molecular mechanisms utilized by PRV to enter host cells is an...