Flavivirus
Virus-Cell InteractionsA Hyperactive Kunjin Virus NS3 Helicase Mutant Demonstrates Increased Dissemination and Mortality in MosquitoesKunjin and West Nile viruses belong to the arthropod-borne flaviviruses, which can result in severe symptoms, including encephalitis, meningitis, and death. Flaviviruses have expanded into new populations and emerged as novel pathogens repeatedly in recent years, demonstrating that they remain a global threat. Currently, there are no approved antiviral therapeutics against either Kunjin or West Nile viruses. Thus, there is a pressing...
Genome Replication and Regulation of Viral Gene Expression | SpotlightZika Virus Subgenomic Flavivirus RNA Generation Requires Cooperativity between Duplicated RNA Structures That Are Essential for Productive Infection in Human CellsFlaviviruses are important emerging and reemerging human pathogens. Understanding the molecular mechanisms for viral replication and evasion of host antiviral responses is relevant to development of control strategies. Flavivirus infections produce viral noncoding RNAs, known as sfRNAs, involved in viral replication and pathogenesis. In this study, we dissected molecular determinants for Zika virus sfRNA generation in the two natural...
Genetic Diversity and Evolution | SpotlightFirst Isolation of a Novel Aquatic Flavivirus from Chinook Salmon (Oncorhynchus tshawytscha) and Its In Vivo Replication in a Piscine Animal ModelChinook salmon are a keystone fish species of great ecological and commercial significance in their native northern Pacific range and in regions to which they have been introduced. Threats to salmon populations include habitat degradation, climate change, and infectious agents, including viruses. While the first isolation of a flavivirus from wild migrating salmon may indicate an emerging disease threat, characterization of the genome...
Virus-Cell InteractionsA Molecular Determinant of West Nile Virus Secretion and Morphology as a Target for Viral AttenuationWest Nile virus (WNV) is a worldwide (re)emerging mosquito-transmitted Flavivirus causing fatal neurological diseases in humans. However, no human vaccine has been yet approved. One of the most effective live-attenuated vaccines was empirically obtained by serial passaging of wild-type yellow fever Flavivirus. However, such an approach is not acceptable nowadays, and the development of a rationally designed vaccine is...
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...
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...
Cellular Response to InfectionBPIFB3 Regulates Endoplasmic Reticulum Morphology To Facilitate Flavivirus ReplicationFlaviviruses and other arthropod-transmitted viruses represent a widespread global health problem, with limited treatment options currently available. Thus, a better understanding of the cellular requirements for their infection is needed. Both DENV and ZIKV rely on expansion of the endoplasmic reticulum (ER) and the induction of autophagy to establish productive infections. However, little is known regarding the interplay between the...
Pathogenesis and ImmunityBasic Amino Acid Substitution at Residue 367 of the Envelope Protein of Tembusu Virus Plays a Critical Role in PathogenesisOutbreaks of Tembusu virus (TMUV) infection have caused huge economic losses in the production of domestic waterfowl since the virus was first recognized in China in 2010. To control TMUV infection, a live-attenuated vaccine candidate of TMUV was developed in our previous study, but the mechanisms of virulence attenuation are not fully understood. Here, we found that the Thr-to-Lys substitution at E367 is a crucial determinant of TMUV...
Genome Replication and Regulation of Viral Gene ExpressionShort Direct Repeats in the 3′ Untranslated Region Are Involved in Subgenomic Flaviviral RNA ProductionFlaviviruses include many important human pathogens. The production of subgenomic flaviviral RNAs (sfRNAs) is important for viral pathogenicity as a common feature of flaviviruses. sfRNAs are formed through the incomplete degradation of viral genomic RNA by the cytoplasmic 5ʹ–3ʹ exoribonuclease Xrn1 halted at the Xrn1-resistant RNA (xrRNA) structures within the 3ʹ-UTR. The 3ʹ-UTRs of the flavivirus genome also contain distinct short...
Pathogenesis and ImmunityLong-Term Protection of Rhesus Macaques from Zika Virus ReinfectionZIKV emerged as a vector-borne pathogen capable of causing illness in infected adults and congenital birth defects in infants born to mothers infected during pregnancy. Despite the decrease in ZIKV cases since the 2015-2016 epidemic, questions concerning the prevalence and longevity of protective immunity have left vulnerable communities fearful that they may become the center of next ZIKV outbreak. Although preexisting herd immunity in...