Influenza A virus replication is dependent on an antioxidant pathway that involves GSH and Bcl‐2

ABSTRACT Growing evidence indicates that viral replication is regulated by the redox state of the host cell. We demonstrate that cells of different origins display differential permissivity for influenza A virus replication, depending on their intracellular redox power as reflected by Bcl‐2 expressi...

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Bibliographic Details
Published in:The FASEB journal 2003-04, Vol.17 (6), p.758-760
Main Authors: Nencioni, Lucia, Iuvara, Alessandra, Aquilano, Katia, Ciriolo, Maria R., Cozzolino, Federico, Rotilio, Giuseppe, Garaci, Enrico, Palamara, Anna T.
Format: Article
Language:English
Subjects:
Animals
Antioxidants - metabolism
Blotting, Western
Cell Line
glutathione
Glutathione - metabolism
Humans
Influenza A virus
Influenza A virus - growth & development
orthomyxovirus
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
redox state
Tumor Cells, Cultured
U937 Cells
viral persistence
Viral Proteins - metabolism
Virus Replication
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Summary:ABSTRACT Growing evidence indicates that viral replication is regulated by the redox state of the host cell. We demonstrate that cells of different origins display differential permissivity for influenza A virus replication, depending on their intracellular redox power as reflected by Bcl‐2 expression and glutathione (GSH) content. Bcl‐2 expressing cells were found to have higher intracellular levels of GSH and to produce lower amounts of virus than Bcl‐2 negative cells. Two different steps in the virus life‐cycle were involved in Bcl‐2/GSH mediated viral inhibition: 1) expression of late viral proteins (in particular hemagglutinin and matrix); and 2) nuclear‐cytoplasmic translocation of viral ribonucleoproteins (vRNPs). Buthionine‐sulfoximine‐induced inhibition of GSH synthesis in Bcl‐2 expressing cells caused an increase in the expression of late viral proteins but did not restore vRNP export to the cytoplasm. Collectively, our findings show that both Bcl‐2 expression and GSH content contribute to the host cell's ability to down‐regulate influenza virus replication, although their effects are exerted at different stages of the viral life‐cycle. In certain cell populations, this form of down‐regulation might conceivably favor the establishment of persistent viral infection.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.02-0508fje