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Influenza A virus replication is dependent on an antioxidant pathway that involves GSH and Bcl‐2
Author(s) -
Nencioni Lucia,
Iuvara Alessandra,
Aquilano Katia,
Ciriolo Maria R.,
Cozzolino Federico,
Rotilio Giuseppe,
Garaci Enrico,
Palamara Anna T.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0508fje
Subject(s) - viral replication , virus , biology , viral life cycle , intracellular , ribonucleoprotein , glutathione , cytoplasm , influenza a virus , nuclear export signal , microbiology and biotechnology , buthionine sulfoximine , virology , viral matrix protein , cell nucleus , gene , biochemistry , rna , enzyme
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.