Control of Apoptosis by Human Cytomegalovirus - Human Cytomegalovirus - page 274

Control of Apoptosis by Human
Cytomegalovirus
A. L. McCormick
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
vMIA Controls Mitochondria-Dependent Death. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283
vICA Controls Caspase-8 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
IE1 491aa , IE2 579aa , and Akt-Dependent Pro-survival Pathways . . . . . . . . . . . . . . . . . . . . . . . . . 287
UL38 Decreases Intrinsic Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
M45 Is a Cell Type-Specific Survival Factor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
m41, Late Infection, and the Golgi Apparatus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
β2.7 and Mitochondrial Respiratory Complex I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
Summary and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Abstract Caspase-dependent apoptosis has an important role in controlling
viruses, and as a result, viruses often encode proteins that target this pathway.
Caspase-dependent apoptosis can be activated from within the infected cell as an
intrinsic response to replication-associated stresses or through death-inducing sig-
nals produced extrinsically by immune cells. Cytomegaloviruses (CMVs) encode
a mitochondria-localized inhibitor of apoptosis, vMIA, and a viral inhibitor of
caspase activation, vICA, the functional homologs of Bcl-2 related and c-FLIP
proteins, respectively. Evidence from viral mutants deleting either vMIA or vICA
suggests that each is necessary and sufficient to promote survival of infected cells
undergoing caspase-dependent apoptosis. Additional proteins, including pUL38,
IE1 491aa , and IE2 579aa , can prevent apoptosis induced by various stimuli, while
viruses with deletions of UL38, M45, or m41 undergo apoptosis. The viral RNA,
β2.7, binds mitochondrial respiratory complex I, maintains ATP production late
in infection, and prevents death induced by a mitochondrial poison. Thus, CMV
A.L. McCornick
Department of Microbiology & Immunology , Emory Vaccine Center , Emory University
Atlanta , GA 30322 , USA
[e-mail]