title: Attenuated strains of influenza A viruses do not induce degradation of RNA polymerase II.
abstract: We have previously shown that infection with laboratory-passaged strains of influenza virus causes both specific degradation of the largest subunit of the RNA polymerase II complex (RNAP II) and inhibition of host cell transcription. When infection with natural human and avian isolates belonging to different antigenic subtypes was examined, we observed that all of these viruses efficiently induce the proteolytic process. To evaluate whether this process is a general feature of nonattenuated viruses, we studied the behavior of the influenza virus strains A/PR8/8/34 (PR8) and the cold-adapted A/Ann Arbor/6/60 (AA), which are currently used as the donor strains for vaccine seeds due to their attenuated phenotype. We have observed that upon infection with these strains, degradation of the RNAP II does not occur. Moreover, by runoff experiments we observe that PR8 has a reduced ability to inhibit cellular mRNA transcription. In addition, a hypervirulent PR8 (hvPR8) variant that multiplies much faster than standard PR8 (lvPR8) in infected cells and is more virulent in mice than the parental PR8 virus, efficiently induces RNAP II degradation. Studies with reassortant viruses containing defined genome segments of both hvPR8 and lvPR8 indicate that PA and PB2 subunits individually contribute to the ability of influenza virus to degrade the RNAP II. In addition, recently it has been reported that the inclusion of PA or PB2 from hvPR8 in lvPR8 recombinant viruses, highly increases their pathogenicity. Together, the data indicate that the capacity of the influenza virus to degrade RNAP II and inhibit the host cell transcription machinery is a feature of influenza A viruses that might contribute to their virulence.
authors.affiliation: Centro Nacional de Biotecnología, CSIC Darwin 3, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Ariel
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Alicia
authors.initials: A
authors.lastname: Pérez-González
authors.forename: M Jaber
authors.initials: MJ
authors.lastname: Hossain
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Chen
authors.forename: Thierry
authors.initials: T
authors.lastname: Rolling
authors.forename: Pilar
authors.initials: P
authors.lastname: Pérez-Breña
authors.forename: Ruben
authors.initials: R
authors.lastname: Donis
authors.forename: Georg
authors.initials: G
authors.lastname: Kochs
authors.forename: Amelia
authors.initials: A
authors.lastname: Nieto
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral; D014158:Transcription, Genetic
chemical_list: D021122:Protein Subunits; D012333:RNA, Messenger; D012367:RNA, Viral; D012319:RNA Polymerase II
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