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Journal of Virology, October 2005, p. 12205-12217, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12205-12217.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mitochondrial Cell Death Suppressors Carried by Human and Murine Cytomegalovirus Confer Resistance to Proteasome Inhibitor-Induced Apoptosis

A. Louise McCormick, Christopher D. Meiering, Geoffrey B. Smith, and Edward S. Mocarski*

Department of Microbiology & Immunology, Fairchild Science Building, Stanford University School of Medicine, Stanford, California 95304-5124

Received 13 June 2005/ Accepted 14 July 2005

Human cytomegalovirus carries a mitochondria-localized inhibitor of apoptosis (vMIA) that is conserved in primate cytomegaloviruses. We find that inactivating mutations within UL37x1, which encodes vMIA, do not substantially affect replication in TownevarATCC (Towne-BAC), a virus that carries a functional copy of the betaherpesvirus-conserved viral inhibitor of caspase 8 activation, the UL36 gene product. In Towne-BAC infection, vMIA reduces susceptibility of infected cells to intrinsic death induced by proteasome inhibition. vMIA is sufficient to confer resistance to proteasome inhibition when expressed independent of viral infection. Murine cytomegalovirus m38.5, whose position in the viral genome is analogous to UL37x1, exhibits mitochondrial association and functions in much the same manner as vMIA in inhibiting intrinsic cell death. This work suggests a common role for vMIA in rodent and primate cytomegaloviruses, modulating the threshold of virus-infected cells to intrinsic cell death.

* Corresponding author. Mailing address: Department of Microbiology & Immunology, Fairchild Science Building, Stanford University School of Medicine, Stanford, CA 95304-5124. Phone: (650) 723-6435. Fax: (650) 723-1606. E-mail: mocarski{at}stanford.edu.

Journal of Virology, October 2005, p. 12205-12217, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12205-12217.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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