Attenuated strains of influenza A viruses do not induce degradation of RNA polymerase II.
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Attenuated strains of influenza A viruses do not induce degradation of RNA polymerase II. / Rodriguez, Ariel; Pérez-González, Alicia; Hossain, M Jaber; Chen, Li-Mei; Rolling, Thierry; Pérez-Breña, Pilar; Donis, Ruben; Kochs, Georg; Nieto, Amelia.
in: J VIROL, Jahrgang 83, Nr. 21, 21, 2009, S. 11166-11174.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Attenuated strains of influenza A viruses do not induce degradation of RNA polymerase II.
AU - Rodriguez, Ariel
AU - Pérez-González, Alicia
AU - Hossain, M Jaber
AU - Chen, Li-Mei
AU - Rolling, Thierry
AU - Pérez-Breña, Pilar
AU - Donis, Ruben
AU - Kochs, Georg
AU - Nieto, Amelia
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Animals
KW - Humans
KW - Mice
KW - Transcription, Genetic
KW - Cell Line
KW - RNA, Messenger/genetics/metabolism
KW - Influenza A virus/genetics/metabolism
KW - Protein Subunits/genetics/metabolism
KW - RNA Polymerase II/genetics/metabolism
KW - RNA, Viral
KW - Animals
KW - Humans
KW - Mice
KW - Transcription, Genetic
KW - Cell Line
KW - RNA, Messenger/genetics/metabolism
KW - Influenza A virus/genetics/metabolism
KW - Protein Subunits/genetics/metabolism
KW - RNA Polymerase II/genetics/metabolism
KW - RNA, Viral
M3 - SCORING: Journal article
VL - 83
SP - 11166
EP - 11174
JO - J VIROL
JF - J VIROL
SN - 0022-538X
IS - 21
M1 - 21
ER -