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Journal of Virology, May 2002, p. 4547-4558, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4547-4558.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Bak and Bax Function To Limit Adenovirus Replication through Apoptosis Induction

Andrea Cuconati,1 Kurt Degenhardt,2,3 Ramya Sundararajan,3 Alan Anschel,3 and Eileen White1,2,3,4*

Howard Hughes Medical Institute,1 Department of Molecular Biology and Biochemistry,2 Center for Advanced Biotechnology and Medicine,4 Cancer Institute of New Jersey,5 Rutgers University, Piscataway, New Jersey 088543

Received 17 December 2001/ Accepted 29 January 2002

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.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Center for Advanced Biotechnology and Medicine, Rutgers University, 679 Hoes Ln., Room 140, Piscataway, NJ 08854. Phone: (732) 235-5329. Fax: (732) 235-5795. E-mail: ewhite{at}cabm.rutgers.edu.

Journal of Virology, May 2002, p. 4547-4558, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4547-4558.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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