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

Virology. 2015 Nov;485:322-9. doi: 10.1016/j.virol.2015.08.009. Epub 2015 Aug 29.

Abstract

Productive arbovirus infections require mechanisms to suppress or circumvent the cellular RNA interference (RNAi) 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.

Keywords: Arbovirus; Dengue virus; Flavivirus; Kunjin virus; Mosquito; RNA interference; SfRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aedes
  • Animals
  • Argonaute Proteins / metabolism
  • Cell Line
  • Cells, Cultured
  • Dengue Virus / genetics
  • Flavivirus / genetics*
  • Gene Knockdown Techniques
  • Gene Silencing
  • Humans
  • RNA Interference*
  • RNA, Small Interfering / genetics
  • RNA, Small Untranslated / genetics*
  • RNA, Viral / genetics*
  • Ribonuclease III / metabolism
  • West Nile virus / genetics

Substances

  • Argonaute Proteins
  • RNA, Small Interfering
  • RNA, Small Untranslated
  • RNA, Viral
  • Ribonuclease III