Disease relevance of NS2

• Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter [1].
• Rescue of synthetic minireplicons establishes the absence of the NS1 and NS2 genes from avian pneumovirus [2].
• To verify this finding, we generated recombinant rabies virus (rRV) expressing either NS1 or NS2 and determined their IFN sensitivity [3].
• Contrary to other unsegmented negative-stranded RNA viruses, a 19-nucleotide intercistronic sequence was present between the NS1 and NS2 genes [4].
• Suppression of the induction of alpha, beta, and lambda interferons by the NS1 and NS2 proteins of human respiratory syncytial virus in human epithelial cells and macrophages [corrected] [5].

High impact information on NS2

• 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 [6].
• 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 [3].
• Thus, RSV has the potential for two transcription programs: one in the absence of M2-1, in which only the NS1 and NS2 genes are transcribed, and one in the presence of M2-1, in which sequential transcription of the complete genome occurs [7].
• Coexpression of the nonstructural NS1 or NS2 protein had little effect on packaging and passage except through indirect effects on RNA synthesis in the initial transfection [8].
• Airway epithelial cells were also infected with equivalent inoculums of RSV without or with single gene deletions of NS1 or NS2 [9].

Biological context of NS2

• 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 [3].
• 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 [10].
• Taken together, our results indicate that NS2 regulates Stat2 levels during RSV infection, thereby modulating viral effects on interferon-dependent gene expression [9].
• Nucleotide sequence analysis of the non-structural NS1 (1C) and NS2 (1B) protein genes of bovine respiratory syncytial virus [10].

Anatomical context of NS2

• The antipeptide antibodies recognized the NS2 protein in the sediment of RSV-infected HEp-2 cells lysed with RIPA buffer at 48 h p.i. The results agree with the reported interaction of RSV with cytoskeletal intermediate filaments [11].

Other interactions of NS2

• In addition, we report the successful recovery of a BRSV mutant lacking the complete NS2 gene, which encodes a nonstructural protein of unknown function [1].

Analytical, diagnostic and therapeutic context of NS2

• The NS2-deficient BRSV replicated autonomously and could be passaged, demonstrating that NS2 is not essential for virus replication in cell culture [1].

References