NS1 Influenza Protein

The NS1 Influenza Protein is created by the internal protein encoding, linear negative-sense, single stranded RNA, NS gene segment; which found in Influenzavirus A, Influenzavirus B and Influenzavirus C; and which also codes for the nuclear export protein or NEP, formerly referred to as the NS2 protein, which mediates the export of vRNPs.^[1]

The influenza protein NS1 is a 26,000 Dalton protein. Human messenger RNA carries a poly(A) tail at the 3' end. NS1 forms a dimer that inhibits the export of poly(A) containing mRNA molecules from the nucleus. This gives preference to viral RNA. NS1 might also inhibit splicing of pre-mRNA by binding to a stem-bulge region in U6 small nuclear RNA (snRNA).^[2] In addition, NS1 is probably able to suppress the interferon response in the virus-infected cell leading to unimpaired virus production.^[3]

NS1 also binds dsRNA. Binding assays with NS1 protein mutants established that the RNA-binding domain of the NS1 protein is required for binding to dsRNA as well as for binding to polyA and U6 snRNA. In addition, dsRNA competed with U6 snRNA for binding to the NS1 protein, a result consistent with both RNAs sharing the same binding site on the protein. As a consequence of its binding to dsRNA, the NS1 protein blocks the activation of the dsRNA-activated protein kinase (PKR) in vitro. This kinase phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (elF-2 alpha), leading to a decrease in the rate of initiation of translation.^[2] In the absence of NS1, this pathway is inhibited during anti-viral response to halt all protein translation - thus stopping the synthesis of viral proteins; however, the influenza virus' NS1 protein is an agent that circumvents host defenses to allows viral gene transcription to occur.

The NS1 protein of the highly pathogenic avian H5N1 viruses circulating in poultry and waterfowl in Southeast Asia is currently believed to be responsible for the enhanced virulence of the strain. H5N1 NS1 is characterized by a single amino acid change at position 92. By changing the amino acid from glutamic acid to aspartic acid, researchers were able to annul the effect of the H5N1 NS1. This single amino acid change in the NS1 gene greatly increased the pathogenicity of the H5N1 influenza virus.^[4]

See also

• H5N1 genetic structure
• Influenza
• NCBI Flu Genome Database

Sources and notes

1. ^ Influenza B and C Virus NEP (NS2) Proteins Possess Nuclear Export Activities Journal of Virology, August 2001, p. 7375-7383, Vol. 75, No. 16
2. ^ ^{a b} Lu, Y et al., 1995. Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylates the elF-2 translation initiation factor. Virology. 1995 Dec 1;214(1):222-8.
3. ^ Kumar, KU, Srivastava, SP, Kaufma,n RJ. 1999. Double-stranded RNA-activated protein kinase (PKR) is negatively regulated by 60S ribosomal subunit protein L18. Mol Cell Biol. 1999 Feb;19(2):1116-25.
4. ^ Novel Avian Influenza H7N3 Strain Outbreak, British Columbia by Martin Hirst et al. Emerging Infectious Diseases Journal from National Center for Infectious Diseases (part of Centers for Disease Control and Prevention) Issue Vol. 10, No. 12 December 2004 (published November 8, 2004)