title: Effects of influenza A virus NS1 protein on protein expression: the NS1 protein enhances translation and is not required for shutoff of host protein synthesis.
abstract: The influenza A virus NS1 protein, a virus-encoded alpha/beta interferon (IFN-alpha/beta) antagonist, appears to be a key regulator of protein expression in infected cells. We now show that NS1 protein expression results in enhancement of reporter gene activity from transfected plasmids. This effect appears to be mediated at the translational level, and it is reminiscent of the activity of the adenoviral virus-associated I (VAI) RNA, a known inhibitor of the antiviral, IFN-induced, PKR protein. To study the effects of the NS1 protein on viral and cellular protein synthesis during influenza A virus infection, we used recombinant influenza viruses lacking the NS1 gene (delNS1) or expressing truncated NS1 proteins. Our results demonstrate that the NS1 protein is required for efficient viral protein synthesis in COS-7 cells. This activity maps to the amino-terminal domain of the NS1 protein, since cells infected with wild-type virus or with a mutant virus expressing a truncated NS1 protein-lacking approximately half of its carboxy-terminal end-showed similar kinetics of viral and cellular protein expression. Interestingly, no major differences in host cell protein synthesis shutoff or in viral protein expression were found among NS1 mutant viruses in Vero cells. Thus, another viral component(s) different from the NS1 protein is responsible for the inhibition of host protein synthesis during viral infection. In contrast to the earlier proposal suggesting that the NS1 protein regulates the levels of spliced M2 mRNA, no effects on M2 protein accumulation were seen in Vero cells infected with delNS1 virus.
authors.affiliation: Department of Microbiology. Immunobiology Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Mirella
authors.initials: M
authors.lastname: Salvatore
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Basler
authors.forename: Jean-Patrick
authors.initials: JP
authors.lastname: Parisien
authors.forename: Curt M
authors.initials: CM
authors.lastname: Horvath
authors.forename: Svetlana
authors.initials: S
authors.lastname: Bourmakina
authors.forename: Hongyong
authors.initials: H
authors.lastname: Zheng
authors.forename: Thomas
authors.initials: T
authors.lastname: Muster
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004285:Dogs; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism* / Q000502:physiology; D008156:Luciferases / Q000235:genetics; D016296:Mutagenesis; D010957:Plasmids; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism; D012367:RNA, Viral; D014709:Vero Cells; D014763:Viral Matrix Proteins / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014764:Viral Proteins / Q000096:biosynthesis; D019892:eIF-2 Kinase / Q000378:metabolism; D000086082:Viroporin Proteins
chemical_list: D008156:Luciferases; D012313:RNA; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D019892:eIF-2 Kinase; C085820:INS1 protein, influenza virus; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C052835:adenovirus associated RNA