Giuseppe
Emeritus
J Virol. 2009 Aug 19. [Epub ahead of print]
Attenuated strains of influenza A viruses do not induce degradation of RNA polymerase II.
Rodriguez A, P?rez-Gonz?lez A, Hossain MJ, Chen LM, Rolling T, P?rez-Bre?a P, Donis R, Kochs G, Nieto A. - Centro Nacional de Biotecnolog?a, C.S.I.C. Darwin 3, Cantoblanco, 28049 Madrid, Spain; Ciber de Enfermedades Respiratorias, Mallorca, Illes Balears, Spain; Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America; Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, 79107 Freiburg, Germany; Influenza and Respiratory Viruses Laboratory, National Center of Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain.
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 these viruses efficiently induce the proteolytic process. To evaluate if this process is a general feature of non-attenuated 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 run-off experiments we observe that PR8 has a reduced ability to inhibit cellular mRNA transcription. In addition, a hyper-virulent 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.
PMID: 19692472 [PubMed - as supplied by publisher]
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Attenuated strains of influenza A viruses do not induce degradation of RNA polymerase II.
Rodriguez A, P?rez-Gonz?lez A, Hossain MJ, Chen LM, Rolling T, P?rez-Bre?a P, Donis R, Kochs G, Nieto A. - Centro Nacional de Biotecnolog?a, C.S.I.C. Darwin 3, Cantoblanco, 28049 Madrid, Spain; Ciber de Enfermedades Respiratorias, Mallorca, Illes Balears, Spain; Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America; Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, 79107 Freiburg, Germany; Influenza and Respiratory Viruses Laboratory, National Center of Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain.
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 these viruses efficiently induce the proteolytic process. To evaluate if this process is a general feature of non-attenuated 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 run-off experiments we observe that PR8 has a reduced ability to inhibit cellular mRNA transcription. In addition, a hyper-virulent 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.
PMID: 19692472 [PubMed - as supplied by publisher]
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