chikungunya virus
Genome Replication and Regulation of Viral Gene ExpressionDesign and Use of Chikungunya Virus Replication Templates Utilizing Mammalian and Mosquito RNA Polymerase I-Mediated TranscriptionChikungunya virus (CHIKV) is a medically important pathogen responsible for recent large-scale epidemics. The development of efficient therapies against CHIKV has been hampered by gaps in our understanding of how nonstructural proteins (nsPs) function to form the viral replicase and replicate virus RNA. Here we describe an extremely sensitive assay to analyze the effects of mutations on the virus RNA synthesis machinery in cells of both...
Vaccines and Antiviral Agents | SpotlightInfectious Chikungunya Virus (CHIKV) with a Complete Capsid Deletion: a New Approach for a CHIKV VaccineCurrently, there is no licensed vaccine against CHIKV infection. An ideal CHIKV vaccine should generate an optimal balance between efficacy and safety. Live attenuated vaccines that can elicit strong immune responses often involve a trade-off of reduced safety. Here, a novel live attenuated vaccine candidate for CHIKV lacking the entire capsid gene, ΔC-CHIKV, was developed. It was demonstrated to be genetically stable, highly attenuated...
Virus-Cell InteractionsNovel Mutations in nsP2 Abolish Chikungunya Virus-Induced Transcriptional Shutoff and Make the Virus Less Cytopathic without Affecting Its Replication RatesChikungunya virus is an important human pathogen which now circulates in both the Old and New Worlds. As in the case of other Old World alphaviruses, CHIKV nsP2 not only has enzymatic functions in viral RNA replication but also is a critical inhibitor of the antiviral response and one of the determinants of CHIKV pathogenesis. In this study, we have applied a new strategy to select a variety of CHIKV nsP2 mutants that no longer...
Genetic Diversity and EvolutionEpidemiological Evidence for Lineage-Specific Differences in the Risk of Inapparent Chikungunya Virus InfectionChikungunya virus (CHIKV) is an understudied threat to human health. During the 2015 chikungunya epidemic in Managua, Nicaragua, we estimated the ratio of symptomatic to asymptomatic CHIKV infections, which is important for understanding transmission dynamics and the public health impact of CHIKV. This index cluster study identified and monitored persons at risk of infection, enabling capture of asymptomatic infections. We estimated...
Virus-Cell InteractionsThe Host DHX9 DExH-Box Helicase Is Recruited to Chikungunya Virus Replication Complexes for Optimal Genomic RNA TranslationThe reemergence of chikungunya virus (CHIKV), an alphavirus that is transmitted to humans by Aedes mosquitoes, is a serious global health threat. In the absence of effective antiviral drugs, CHIKV infection has a significant impact on human health, with chronic arthritis being one of the most serious complications. The molecular understanding of host-virus interactions is a prerequisite to the development of targeted...
Genetic Diversity and EvolutionChikungunya Virus Fidelity Variants Exhibit Differential Attenuation and Population Diversity in Cell Culture and Adult MiceCHIKV is a reemerging global health threat that elicits debilitating arthritis in humans. There are currently no commercially available CHIKV vaccines. Like other RNA viruses, CHIKV has a high mutation rate and is capable of rapid intrahost diversification during an infection. In other RNA viruses, virus population diversity associates with disease progression; however, potential impacts of intrahost viral diversity on CHIKV arthritic...
Virus-Cell InteractionsSindbis Virus Infection Causes Cell Death by nsP2-Induced Transcriptional Shutoff or by nsP3-Dependent Translational ShutoffAlphaviruses are a group of important human and animal pathogens with worldwide distribution. Their characteristic feature is a highly cytopathic phenotype in cells of vertebrate origin. The molecular mechanism of CPE remains poorly understood. In this study, by using Sindbis virus (SINV) as a model of the Old World alphaviruses, we demonstrated that SINV-specific CPE is redundantly determined by viral nsP2 and nsP3 proteins. NsP2...
- Virus-Cell Interactions | SpotlightMultiple Host Factors Interact with the Hypervariable Domain of Chikungunya Virus nsP3 and Determine Viral Replication in Cell-Specific Mode
Alphaviruses utilize a broad spectrum of cellular factors for efficient formation and function of replication complexes (RCs). Our data demonstrate for the first time that the hypervariable domain (HVD) of chikungunya virus nonstructural protein 3 (nsP3) is intrinsically disordered. It binds at least 3 families of cellular proteins, which play an indispensable role in viral RNA replication. The proteins of each family demonstrate...
- Vaccines and Antiviral AgentsEmerging Alphaviruses Are Sensitive to Cellular States Induced by a Novel Small-Molecule Agonist of the STING Pathway
- Pathogenesis and Immunity | SpotlightInterferon Regulatory Factor 1 Protects against Chikungunya Virus-Induced Immunopathology by Restricting Infection in Muscle Cells