Bcl-2 expression and p38MAPK activity in cells infected with influenza A virus: impact on virally induced apoptosis and viral replication (Articolo in rivista)

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  • Bcl-2 expression and p38MAPK activity in cells infected with influenza A virus: impact on virally induced apoptosis and viral replication (Articolo in rivista) (literal)
Anno
  • 2009-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1074/jbc.M900146200 (literal)
Alternative label
  • Nencioni L. 1*; De Chiara G. 3*; Sgarbanti R. 1; Amatore D. 1; Aquilano K. 4; Marcocci M.E. 1; Serafino A. 6; Torcia M. 7; Cozzolino F. 7; Ciriolo M.R. 4,8; Garaci E.5; Palamara A.T. 8,2 (2009)
    Bcl-2 expression and p38MAPK activity in cells infected with influenza A virus: impact on virally induced apoptosis and viral replication
    in Journal of biological chemistry (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Nencioni L. 1*; De Chiara G. 3*; Sgarbanti R. 1; Amatore D. 1; Aquilano K. 4; Marcocci M.E. 1; Serafino A. 6; Torcia M. 7; Cozzolino F. 7; Ciriolo M.R. 4,8; Garaci E.5; Palamara A.T. 8,2 (literal)
Pagina inizio
  • 16004 (literal)
Pagina fine
  • 16015 (literal)
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  • Impact Factor (2009): 5,52 (literal)
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  • 284 (literal)
Rivista
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  • 23 (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • 1 - Department of Public Health Sciences and 2 - Istituto Pasteur-Fondazione Cenci Bolognetti, “Sapienza” University of Rome, 00185 Rome, Italy; 3 - Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy; 4 - Departments of Biology and 5 - Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata,” 00133 Rome; 6 - Institute of Neurobiology and Molecular Medicine, Consiglio Nazionale delle Ricerche, 00133 Rome; 7 - Department of Clinical Physiopathology, University of Florence, 50139 Florence, Italy; 8 - Scientific Institute for Research, Hospitalization, and Health Care “S. Raffaele,” 00100 Rome, Italy. * Both authors contributed equally to this work. (literal)
Titolo
  • Bcl-2 expression and p38MAPK activity in cells infected with influenza A virus: impact on virally induced apoptosis and viral replication (literal)
Abstract
  • Previous reports have shown that various steps in the influenza A virus life cycle are impaired in cells expressing the antiapoptotic protein Bcl-2 (Bcl-2(+) cells). We demonstrated a direct link between Bcl-2 and the reduced nuclear export of viral ribonucleoprotein (vRNP) complexes in these cells. However, despite its negative impact on viral replication, Bcl-2 did not prevent host cells from undergoing virally triggered apoptosis. The protein's reduced antiapoptotic capacity was related to phosphorylation of its threonine 56 and serine 87 residues by virally activated p38MAPK. In infected Bcl-2(+) cells, activated p38MAPK was found predominantly in the cytoplasm, colocalized with Bcl-2, and both Bcl-2 phosphorylation and virally induced apoptosis were diminished by specific inhibition of p38MAPK activity. In contrast, in Bcl-2-negative (Bcl-2(-)) cells, which are fully permissive to viral infection, p38MAPK activity was predominantly nuclear, and its inhibition decreased vRNP traffic, phosphorylation of viral nucleoprotein, and virus titers in cell supernatants, suggesting that this kinase also contributes to the regulation of vRNP export and viral replication. This could explain why in Bcl-2(+) cells, where p38MAPK is active in the cytoplasm, phosphorylating Bcl-2, influenza viral replication is substantially reduced, whereas apoptosis proceeds at rates similar to those observed in Bcl-2(-) cells. Our findings suggest that the impact of p38MAPK on the influenza virus life cycle and the apoptotic response of host cells to infection depends on whether or not the cells express Bcl-2, highlighting the possibility that the pathological effects of the virus are partly determined by the cell type it targets (literal)
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