Interaction of TIA-1/TIAR with West Nile and dengue virus products in infected cells interferes with stress granule formation and processing body assembly.
The West Nile virus minus-strand 3' terminal stem loop (SL) RNA was previously shown to bind specifically to cellular stress granule (SG) components, T cell intracellular antigen-1 (TIA-1) and the related protein TIAR. In vitro TIAR binding was 10 times more efficient than TIA-1. The 3'(-)SL functions as the promoter for genomic RNA synthesis. Colocalization of TIAR and TIA-1 with the viral replication complex components dsRNA and NS3 was observed in the perinuclear regions of West Nile virus- and dengue virus-infected cells. The kinetics of accumulation of TIAR in the perinuclear region was similar to those of genomic RNA synthesis. In contrast, relocation of TIA-1 to the perinuclear region began only after maximal levels of RNA synthesis had been achieved, except when TIAR was absent. Virus infection did not induce SGs and progressive resistance to SG induction by arsenite developed coincident with TIAR relocation. A progressive decrease in the number of processing bodies was secondarily observed in infected cells. These data suggest that the interaction of TIAR with viral components facilitates flavivirus genome RNA synthesis and inhibits SG formation, which prevents the shutoff of host translation.
Emara
Mohamed M
MM
Department of Biology, Georgia State University, Atlanta, GA 30302, USA.
Brinton
Margo A
MA
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003594:Cytoplasmic Granules / Q000378:metabolism*; D003716:Dengue Virus / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D011485:Protein Binding; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication; D014902:West Nile virus / Q000502:physiology*
D039102:Poly(A)-Binding Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014764:Viral Proteins