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.