title: Differential effects of NS1 proteins of human pandemic H1N1/2009, avian highly pathogenic H5N1, and low pathogenic H5N2 influenza A viruses on cellular pre-mRNA polyadenylation and mRNA translation.
abstract: The nonstructural protein NS1 of influenza A virus blocks the development of host antiviral responses by inhibiting polyadenylation of cellular pre-mRNA. NS1 also promotes the synthesis of viral proteins by stimulating mRNA translation. Here, we show that recombinant NS1 proteins of human pandemic H1N1/2009, avian highly pathogenic H5N1, and low pathogenic H5N2 influenza strains differentially affected these two cellular processes: NS1 of the two avian strains, in contrast to NS1 of H1N1/2009, stimulated translation of reporter mRNA in cell-free translation system; NS1 of H5N1 was an effective inhibitor of cellular pre-mRNA polyadenylation in A549 cells, unlike NS1 of H5N2 and H1N1/2009. We identified key amino acids in NS1 that contribute to its activity in these two basic cellular processes. Thus, we identified strain-specific differences between influenza virus NS1 proteins in pre-mRNA polyadenylation and mRNA translation.
authors.affiliation: Institute of Immunology, Centre de Recherche Public-Santé/Laboratoire National de Santé, L-1011, Luxembourg.
authors.forename: Denis E
authors.initials: DE
authors.lastname: Kainov
authors.forename: Konstantin H
authors.initials: KH
authors.lastname: Müller
authors.forename: Linda L
authors.initials: LL
authors.lastname: Theisen
authors.forename: Maria
authors.initials: M
authors.lastname: Anastasina
authors.forename: Minttu
authors.initials: M
authors.lastname: Kaloinen
authors.forename: Claude P
authors.initials: CP
authors.lastname: Muller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000472:pathogenicity; D053125:Influenza A Virus, H5N2 Subtype / Q000235:genetics / Q000472:pathogenicity; D009980:Influenza A virus / Q000235:genetics* / Q000472:pathogenicity; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000453:epidemiology / Q000503:physiopathology / Q000821:virology*; D058873:Pandemics; D026723:Polyadenylation / Q000502:physiology; D014176:Protein Biosynthesis / Q000502:physiology*; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D012322:RNA Precursors / Q000378:metabolism; D013045:Species Specificity; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014774:Virulence
chemical_list: C085820:INS1 protein, influenza virus; D012322:RNA Precursors; D017361:Viral Nonstructural Proteins