Flavivirus sfRNA suppresses antiviral RNA interference in cultured cells and mosquitoes and directly interacts with the RNAi machinery

Autor(es): Moon, Stephanie L.; Dodd, Benjamin J. T.; Brackney, Doug E.; Wilusz, Carol J.; Ebel, Gregory D.; Wilusz, Jeffrey


Resumo: Productive arbovirus infections require mechanisms to suppress or circumvent the cellular RNA interference (RNA pathway, a major antiviral response in mosquitoes. In this study, we demonstrate that two flaviviruses, Dengue virus and Kunjin virus, significantly repress siRNA-mediated RNAi in infected human cells as well as during infection of the mosquito vector Culex quinquefasciatus. Arthropod-borne flaviviruses generate a small structured non-coding RNA from the viral 3' UTR referred to as sfRNA. Analysis of infections with a mutant Kunjin virus that is unable to generate appreciable amounts of the major sfRNA species indicated that RNAi suppression was associated with the generation of the non-coding sfRNA. Co-immunoprecipitation of sfRNA with RNAi mediators Dicer and Ago2 suggest a model for RNAi suppression. Collectively, these data help to establish a clear role for sfRNA in RNAi suppression and adds to the emerging impact of viral long non-coding RNAs in modulating aspects of anti-viral immune processes. (C) 2015 Elsevier Inc. All rights reserved.


Palavras-Chave: Flavivirus; Dengue virus; Kunjin virus; RNA interference; SfRNA; Mosquito; Arbovirus


Imprenta: Virology, v. 485, p. 322-329, 2015


Identificador do objeto digital: 10.1016/j.virol.2015.08.009


Descritores: Aedes aegypti - Cell ; Aedes aegypti - Immune response ; Aedes aegypti - Molecular structure ; Aedes aegypti - RNA ; Aedes aegypti - Viral infections ; Aedes aegypti - Virus


Data de publicação: 2015