Insights into the role of the non-structural protein 2 (NS2) in Bluetongue virus morphogenesis.

Bluetongue virus (BTV) non-structural protein 2 (NS2) belongs to a class of highly conserved proteins found in Orbiviruses of the Reoviridae family. NS2 forms large multimeric complexes and localizes to cytoplasmic inclusions in infected cells. Due to its ability to bind single-stranded RNA (ssRNA), it has been suggested that the protein participates in the selection and sequestration of the 10 different BTV-ssRNA segments, prior to their encapsidation and conversion into the BTV double-stranded RNA (dsRNA) genome. Recent advances in understanding how BTV-NS2 is organized and functions are largely inferred from structural studies. The X-ray crystal structure of the N-terminal domain of NS2 suggests that the full-length protein could assemble as homomultimers of maximally 10-11 subunits. The crystallographic structural information combined with small-angle X-ray scattering experiments on the C-terminal domain as well as negative-stain electron microscopy on the full-length protein give us a first glimpse of how the two protein domains associate and function. Herein, we survey biochemical and recent structural investigations on NS2 important to the understanding of the molecular events underlying the process of BTV morphogenesis. We also present a phylogenetic analysis of the NS2 sequences.