Giuseppe
Emeritus
J Virol. 2009 Jun 3. [Epub ahead of print]
Lack of Bax Prevents Influenza A-Induced Apoptosis and Causes Diminished Viral Replication.
McLean JE, Datan E, Matassov D, Zakeri ZF. Department of Biology, Queens College and Graduate Center of the City University of New York, Flushing, New York 11367, USA.
Ectopic overexpression of Bcl-2 restricts both Influenza A virus-induced apoptosis and Influenza A virus replication in MDCK cells, thus suggesting a role for Bcl-2 family members during infection. Here we report that Influenza A virus cannot establish an apoptotic response without functional Bax, a downstream target of Bcl-2, and that both Bax and Bak are directly involved in Influenza A replication and virus-induced cell death.
Bak is substantially downregulated during Influenza A infection in MDCK cells, and knockout of Bak in mouse embryonic fibroblasts yields a dramatic rise in the rate of apoptotic death and a corresponding increase in virus replication, suggesting that Bak suppresses both apoptosis and replication of virus and that the virus suppresses Bak.., Bax, however, is activated and translocates from the cytosol to the mitochondria; this activation is required for efficient induction of apoptosis and virus replication.
Knockout of Bax in mouse embryonic fibroblasts blocks induction of apoptosis, restricts infection-mediated activation of executioner caspases, and inhibits virus propagation. Bax knockout cells still die, though by an alternative death pathway displaying characteristics of autophagy, similar to our earlier observation that Influenza A infection in the presence of a pan-caspase inhibitor leads to an increase in autophagy.
Knockout of Bax causes retention of Influenza A NP protein within the nucleus. We conclude that cell and virus struggle to control apoptosis and autophagy, as appropriately-timed apoptosis is important for replication of Influenza A virus.
PMID: 19494020 [PubMed - as supplied by publisher]
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Lack of Bax Prevents Influenza A-Induced Apoptosis and Causes Diminished Viral Replication.
McLean JE, Datan E, Matassov D, Zakeri ZF. Department of Biology, Queens College and Graduate Center of the City University of New York, Flushing, New York 11367, USA.
Ectopic overexpression of Bcl-2 restricts both Influenza A virus-induced apoptosis and Influenza A virus replication in MDCK cells, thus suggesting a role for Bcl-2 family members during infection. Here we report that Influenza A virus cannot establish an apoptotic response without functional Bax, a downstream target of Bcl-2, and that both Bax and Bak are directly involved in Influenza A replication and virus-induced cell death.
Bak is substantially downregulated during Influenza A infection in MDCK cells, and knockout of Bak in mouse embryonic fibroblasts yields a dramatic rise in the rate of apoptotic death and a corresponding increase in virus replication, suggesting that Bak suppresses both apoptosis and replication of virus and that the virus suppresses Bak.., Bax, however, is activated and translocates from the cytosol to the mitochondria; this activation is required for efficient induction of apoptosis and virus replication.
Knockout of Bax in mouse embryonic fibroblasts blocks induction of apoptosis, restricts infection-mediated activation of executioner caspases, and inhibits virus propagation. Bax knockout cells still die, though by an alternative death pathway displaying characteristics of autophagy, similar to our earlier observation that Influenza A infection in the presence of a pan-caspase inhibitor leads to an increase in autophagy.
Knockout of Bax causes retention of Influenza A NP protein within the nucleus. We conclude that cell and virus struggle to control apoptosis and autophagy, as appropriately-timed apoptosis is important for replication of Influenza A virus.
PMID: 19494020 [PubMed - as supplied by publisher]
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