Control of Apoptosis by Human Cytomegalovirus - Human Cytomegalovirus - page 278

Fig. 2 A representation of the apoptosis pathway and CMV-mediated alterations preventing
death, as described in the text. Dashed arrows indicate events prevented by the viral proteins,
vICA or vMIA, as indicated. The solid arrow indicates vMIA-dependent relocalization of Bax to
mitochondria. At mitochondria, a complex(s) of proteins including Bax as an oligomer, vMIA,
GADD45, and Bcl-x L prevents the release of mitochondrial protein cytochrome c. vICA binds
procaspase-8 and is depicted as a complex that prevents procaspase-8 activation following addi-
tion of extrinsic death signals. The mechanisms and/or direct physical interactions that promote
survival in the presence of the remaining viral proteins, pUL38, IE1 491aa , IE2 579aa , M45, and m41
are unclear, and these are placed according to the anticipated site of localization within the cell.
For simplicity, many important regulatory components have not been included
of Bax at mitochondria has also been suggested as the mechanism (Karbowski
et al. 2006) for vMIA-dependent disruption of reticular mitochondrial networks
(McCormick et al. 2003b); however, more recent evidence of vMIA mutants
that disrupt networks but fail to bind Bax (Pauleau et al. 2007) suggests other
factors may also be important.
vMIA prevents apoptosis during infection; however, vMIA is not required for
replication, and replication in the absence of vMIA does not induce caspase-
dependent apoptosis (McCormick et al. 2005). A vMIA deletion mutant made in
the laboratory-propagated strain, Towne var ATCC, produces yields nearly equiva-
lent to parental virus. In contrast, vMIA is more critical for efficient replication of
the laboratory strain AD169 var ATCC (Reboredo et al. 2004). These strain-
dependent variations may suggest that the quantity or quality of intrinsic stresses