Abstract
AbstractOne-third of the nine WHO shortlisted pathogens prioritized for research and development in public health emergencies belong to theBunyaviralesorder. SeveralBunyaviralesspecies carry an NSm protein that acts as a virulence factor. We predicted the structures of these NSm protein and unexpectedly found that in two families, its cytosolic domain is inferred to have a similar fold to the cytosolic domain of the viral envelope-forming glycoprotein N (Gncyto) encoded on the same genome fragment. We show that although the sequence identity between the NSmcytoand Gncytodomains is low, the conservation of the two zinc finger-forming CCHC motifs explains the predicted structural conservation. Importantly, our predictions provide a first glimpse into the long unknown structure of NSm and its link to virulence. Also, these predictions suggest that NSm is the result of a gene duplication event in theBunyavirales NairoviridaeandPeribunyaviridaefamilies, and that such events may be common in the recent evolutionary history of RNA viruses.
Publisher
Cold Spring Harbor Laboratory