structure analysis of alphaviral RNA genomes shows diversity in the evasion of IFIT1-mediated innate immunity.

The IFIT (interferon-induced proteins with tetratricopeptide repeats) family constitutes a major arm of the antiviral function of type I interferon (IFN). Human IFIT1, the earliest discovered member of this family, inhibits several viruses of positivestrand RNA genome. IFIT1 specifically recognizes single-stranded RNAwith canonical 7-methylguanylate cap at the 50 end (Cap0), and inhibits their translation by competing with eIF4E (eukaryotic initiation factor 4E), an essential factor for 50Cap recognition. Recently, a novel viral mechanism of IFIT1 suppression was reported, in which an RNA hairpin in the 50 untranslated region (50UTR) of the viral genome prevented recognition by IFIT1 and enhanced virus growth. Here, I have analyzed the in silico predicted structures in the 50UTR of the genomes of the Alphaviruses, a large group of enveloped RNA virus with positive-sense single-stranded genome. The results uncovered a large ensemble of RNA secondary structures of diverse size and shape in the different viruses, which showed little correspondence to the phylogeny of the viruses. Unexpectedly, the 50UTR of several viral genomes in this family did not fold into any structure, suggesting either their extreme sensitivity to IFIT1 or the existence of alternative viral mechanisms of subverting IFIT1 function.