A viral RNA structural element alters host recognition of nonself RNA.
Although interferon (IFN) signaling induces genes that limit viral infection, many pathogenic viruses overcome this host response. As an example, 2'-O methylation of the 5' cap of viral RNA subverts mammalian antiviral responses by evading restriction of Ifit1, an IFN-stimulated gene that regulates protein synthesis. However, alphaviruses replicate efficiently in cells expressing Ifit1 even though their genomic RNA has a 5' cap lacking 2'-O methylation. We show that pathogenic alphaviruses use secondary structural motifs within the 5' untranslated region (UTR) of their RNA to alter Ifit1 binding and function. Mutations within the 5'-UTR affecting RNA structural elements enabled restriction by or antagonism of Ifit1 in vitro and in vivo. These results identify an evasion mechanism by which viruses use RNA structural motifs to avoid immune restriction.
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jennifer L
JL
Hyde
Christina L
CL
Gardner
Taishi
T
Kimura
James P
JP
White
Gai
G
Liu
Derek W
DW
Trobaugh
Cheng
C
Huang
Marco
M
Tonelli
Slobodan
S
Paessler
Kiyoshi
K
Takeda
William B
WB
Klimstra
Gaya K
GK
Amarasinghe
Michael S
MS
Diamond
D020121:5' Untranslated Regions / Q000276:immunology; D048868:Adaptor Proteins, Signal Transducing; D000524:Alphavirus / Q000472:pathogenicity* / Q000502:physiology; D018354:Alphavirus Infections / Q000276:immunology* / Q000821:virology; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D009690:Nucleic Acid Conformation; D012315:RNA Caps / Q000737:chemistry* / Q000276:immunology*; D012367:RNA, Viral / Q000737:chemistry* / Q000276:immunology*; D016601:RNA-Binding Proteins; D014779:Virus Replication
D020121:5' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C092573:Ifit1 protein, mouse; D012315:RNA Caps; D012367:RNA, Viral; D016601:RNA-Binding Proteins