Disease relevance of NS1

• Nucleotide sequence analysis of the non-structural NS1 (1C) and NS2 (1B) protein genes of bovine respiratory syncytial virus [1].
• Comparison of the NS1 gene of BRSV with the corresponding sequences of ovine respiratory syncytial virus (ORSV) and human respiratory syncytial virus (HRSV) subgroups A and B revealed 82, 67 and 65% identity at the nucleotide level, and 89, 69 and 68% identity at the amino acid level, respectively [1].
• To verify this finding, we generated recombinant rabies virus (rRV) expressing either NS1 or NS2 and determined their IFN sensitivity [2].

High impact information on NS1

• In contrast, infection with recombinant BRSVs lacking either or both NS genes resulted in efficient upregulation of ISGs [3].
• These results suggest that the NS proteins block the induction of IFN-alpha/beta gene expression and thereby increase the virulence of BRSV [4].
• Here we demonstrate that, in contrast to wild-type BRSVs, recombinant BRSVs (rBRSVs) lacking the NS proteins, and those lacking NS2 in particular, are strong inducers of IFN-alpha/beta in bovine nasal fibroblasts and bronchoalveolar macrophages [4].

Biological context of NS1

• The NS1 and NS2 genes were 524 and 489 nucleotides long with single open reading frames, encoding polypeptides of 136 and 124 amino acids, respectively [1].
• In cells coinfected with NS1- and NS2-expressing rRVs, virus replication was resistant to doses of IFN which caused a 1,000-fold reduction of replication in cells infected with wild-type RV or with each of the NS-expressing rRVs alone [2].
• The functions of bovine respiratory syncytial virus (BRSV) nonstructural proteins NS1 and NS2 were studied by generation and analysis of recombinant BRSV carrying single and double gene deletions [2].

Other interactions of NS1

• In addition, we report the successful recovery of a BRSV mutant lacking the complete NS2 gene, which encodes a nonstructural protein of unknown function [5].

References