This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Rodriguez, A.
Right arrow Articles by Nieto, A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rodriguez, A.
Right arrow Articles by Nieto, A.

 Previous Article  |  Next Article 

Journal of Virology, November 2009, p. 11166-11174, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.01439-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Attenuated Strains of Influenza A Viruses Do Not Induce Degradation of RNA Polymerase II{triangledown}

Ariel Rodriguez,1,2 Alicia Pérez-González,1,2 M. Jaber Hossain,3 Li-Mei Chen,3 Thierry Rolling,4 Pilar Pérez-Breña,5 Ruben Donis,3 Georg Kochs,4 and Amelia Nieto1,2*

Centro Nacional de Biotecnología, CSIC Darwin 3, Cantoblanco, 28049 Madrid, Spain,1 Ciber de Enfermedades Respiratorias, Mallorca, Illes Balears, Spain,2 Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia,3 Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, 79107 Freiburg, Germany,4 Influenza and Respiratory Viruses Laboratory, National Center of Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain5

Received 13 July 2009/ Accepted 7 August 2009

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.

* Corresponding author. Mailing address: Centro Nacional de Biotecnología, CSIC Darwin 3, Cantoblanco, 28049 Madrid, Spain. Phone: 34 91 5854914. Fax: 34 91 5854506. E-mail: anieto{at}cnb.csic.es

{triangledown} Published ahead of print on 19 August 2009.

Journal of Virology, November 2009, p. 11166-11174, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.01439-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»