title: West nile virus infections suppress early viral RNA synthesis and avoid inducing the cell stress granule response.
abstract: West Nile virus (WNV) recently became endemic in the United States and is a significant cause of human morbidity and mortality. Natural WNV strain infections do not induce stress granules (SGs), while W956IC (a lineage 2/1 chimeric WNV infectious clone) virus infections produce high levels of early viral RNA and efficiently induce SGs through protein kinase R (PKR) activation. Additional WNV chimeric viruses made by replacing one or more W956IC genes with the lineage 1 Eg101 equivalent in the W956IC backbone were analyzed. The Eg-NS4b+5, Eg-NS1+3+4a, and Eg-NS1+4b+5 chimeras produced low levels of viral RNA at early times of infection and inefficiently induced SGs, suggesting the possibility that interactions between viral nonstructural proteins and/or between viral nonstructural proteins and cell proteins are involved in suppressing early viral RNA synthesis and membrane remodeling during natural WNV strain infections. Detection of exposed viral double-stranded RNA (dsRNA) in W956IC-infected cells suggested that the enhanced early viral RNA synthesis surpassed the available virus-induced membrane protection and allowed viral dsRNA to activate PKR.
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia, USA. mbrinton@gsu.edu
authors.forename: S C
authors.initials: SC
authors.lastname: Courtney
authors.forename: S V
authors.initials: SV
authors.lastname: Scherbik
authors.forename: B M
authors.initials: BM
authors.lastname: Stockman
authors.forename: M A
authors.initials: MA
authors.lastname: Brinton
mesh_terms: D002460:Cell Line; D006801:Humans; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014901:West Nile Fever / Q000201:enzymology / Q000503:physiopathology* / Q000821:virology*; D014902:West Nile virus / Q000235:genetics* / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins; D019892:eIF-2 Kinase