Bak and Bax function to limit adenovirus replication through apoptosis induction.

Abstract:

:Adenovirus infection and expression of E1A induces both proliferation and apoptosis, the latter of which is blocked by the adenovirus Bcl-2 homologue E1B 19K. The mechanism of apoptosis induction and the role that it plays in productive infection are not known. Unlike apoptosis mediated by death receptors, infection with proapoptotic E1B 19K mutant viruses did not induce cleavage of Bid but nonetheless induced changes in Bak and Bax conformation, Bak-Bax interaction, caspase 9 and 3 activation, and apoptosis. In wild-type-adenovirus-infected cells, in which E1B 19K inhibits apoptosis, E1B 19K was bound to Bak, precluding Bak-Bax interaction and changes in Bax conformation. Infection with E1B 19K mutant viruses induced apoptosis in wild-type and Bax- or Bak-deficient baby mouse kidney cells but not in those deficient for both Bax and Bak. Furthermore, Bax and Bak deficiency dramatically increased E1A expression and virus replication. Thus, Bax- and Bak-mediated apoptosis severely limits adenoviral replication, demonstrating that Bax and Bak function as an antiviral response at the cellular level.

journal_name

J Virol

journal_title

Journal of virology

authors

Cuconati A,Degenhardt K,Sundararajan R,Anschel A,White E

doi

10.1128/jvi.76.9.4547-4558.2002

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

4547-58

issue

9

eissn

0022-538X

issn

1098-5514

journal_volume

76

pub_type

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