Biology Reference
In-Depth Information
organs, they regulate the dynamic shape and intraluminal pressure of these
organs and help in maintaining organ integrity. Smooth muscle cells are
susceptible to productive HCMV infection (Tumilowicz et al. 1985), which
may have important pathophysiological consequences. When the host's
immune response is severely compromised, focal expansion with subsequent
lytic replication in the gastrointestinal tract can result in ulceration (Sinzger
et al. 1995) and perforation (Genta et al. 1993), with sometimes fatal outcome.
In the immunocompetent host, infection of vascular smooth muscle cells may
be pathogenetically important. In these cells, HCMV downregulates extracel-
lular matrix proteins, which may contribute to the development of inflamma-
tory vasculopathies (Reinhardt et al. 2006). In addition, lytic infection of
vascular smooth muscle cells might provoke a response to injury reaction, and
consequently HCMV is considered a possible pathogenetic (co)factor in the
context of atherosclerosis (Stassen et al. 2006).
Endothelial Cells
Speculation on an association of HCMV with vascular damage is additionally
supported by the marked endothelial cell tropism of HCMV in vivo. Again, the
ubiquitous distribution of small vessels throughout the body is reflected by the
detection of HCMV-infected microvascular endothelial cells in various organs,
e.g., brain, lung, liver, kidney and the complete gastrointestinal tract (Myerson
et al. 1984; Wiley and Nelson 1988; Roberts et al. 1989; Sinzger et al. 1995;
Bissinger et al. 2004). They support productive lytic infection and can hence
promote hematogenous dissemination HCMV from the circulating blood into
organ tissues, often accompanied by a vasculitic response around infected ves-
sel walls (Roberts et al. 1989; Sinzger et al. 1995). Macrovascular endothelial
cells are also susceptible to productive lytic infection (Kahl et al. 2000) and
combined damage of the endothelial layer and the underlying smooth muscle
layer may initiate the cascade of defense reactions finally resulting in vascular
lesions. While the contribution of HCMV to atherosclerosis in the general
population is still a matter of debate (see also the chapter by D.N. Streblow,
this volume), the association is very clear in patients after heart transplantation
(Valantine 2004; Potena et al. 2006).
Leukocytes
The disposition of HCMV to systemic dissemination and multiorgan involvement
has already been mentioned. Leukocytes are assumed to be a central player with
regard to hematogenous spread of the virus, whether by being a target of permissive
