Flavivirus sfRNA suppresses antiviral RNA interference in cultured cells and mosquitoes and directly interacts with the RNAi machinery.
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.
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Stephanie L
SL
Moon
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Benjamin J T
BJ
Dodd
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Doug E
DE
Brackney
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Carol J
CJ
Wilusz
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Gregory D
GD
Ebel
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA. Electronic address: jeffrey.wilusz@colostate.edu.
Jeffrey
J
Wilusz
D000330:Aedes; D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003716:Dengue Virus / Q000235:genetics; D005416:Flavivirus / Q000235:genetics*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D058727:RNA, Small Untranslated / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D043244:Ribonuclease III / Q000378:metabolism; D014902:West Nile virus / Q000235:genetics
D060565:Argonaute Proteins; D034741:RNA, Small Interfering; D058727:RNA, Small Untranslated; D012367:RNA, Viral; D043244:Ribonuclease III
Arbovirus; Dengue virus; Flavivirus; Kunjin virus; Mosquito; RNA interference; SfRNA