Disease relevance of NS2

• Altered growth characteristics of recombinant respiratory syncytial viruses which do not produce NS2 protein [1].
• The NS2 protein of human respiratory syncytial virus suppresses the cytotoxic T-cell response as a consequence of suppressing the type I interferon response [2].
• The NS2 knockout antigenomic cDNAs were cotransfected with plasmids encoding the N, P, L, and M2-1 proteins of RSV, each controlled by the T7 promoter, into cells infected with a vaccinia virus recombinant expressing T7 RNA polymerase [1].

High impact information on NS2

• Finally, recombinantly expressed NS1 and NS2, individually and together, reduced apoptosis by tumor necrosis factor alpha, suggesting an intrinsic antiapoptotic property of both [3].
• We have now found that the HRSV NS2 protein strongly controls IFN induction in mouse cells in vitro, validating the use of the mouse model to study the consequences of these gene deletions on host immunity [2].
• Recombinant respiratory syncytial virus bearing a deletion of either the NS2 or SH gene is attenuated in chimpanzees [4].
• To study the function of NS2, we have used a recently developed reverse genetics system to ablate expression of NS2 in recombinant RSV [1].
• Upon passage, the NS2stop virus stock rapidly developed revertants which expressed NS2 protein and grew with similar plaque morphology and kinetics wild-type RSV [1].

Biological context of NS2

• A full-length cDNA copy of the antigenome of RSV A2 strain under the control of a T7 promoter was modified by introduction of tandem termination codons within the NS2 open reading frame (NS2stop) or by deletion of the entire NS2 gene (DeltaNS2) [1].

Other interactions of NS2

• These findings demonstrate that a recombinant RSV mutant lacking either the NS2 or SH gene is attenuated and indicate that these deletions may be useful as attenuating mutations in new, live recombinant RSV vaccine candidates for both pediatric and elderly populations [4].

Analytical, diagnostic and therapeutic context of NS2

• These results show that the NS2 protein is not essential for RSV replication, although its presence greatly improves virus growth in cell culture [1].
• Using ELISA, 50% effective concentration (EC50) values were about 0.5-1 microM for an antisense oligonucleotide targeted to the start of the NS2 gene [5].

References