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et al. 1989; Schwartz et al. 1990; Grefte et al. 1993). Likewise, detection of late
structural viral proteins in infected cells argues in the same direction, and the
combination of the latter approach with the additional detection of cell marker
proteins allowed for a reliable identification of the respective cell types (Sinzger
et al. 1993, 1996, 1999a; Digel and Sinzger 2006). Together with the often focal
distribution of clusters of infected cells this provided strong evidence that mucosal
epithelial cells, connective tissue cells, smooth muscle cells and endothelial cells
can produce and transmit viral progeny to their environment (Fig. 1a). HCMV
replication can be detected in almost every organ during acute infection under
certain conditions, e.g., severe cases of intrauterine infection (Bissinger et al.
2002). Liver, gastrointestinal tract, lung, retina and brain are predominant sites
of clinical manifestations of HCMV infections in immunocompromised hosts
(Plachter et al. 1996). Within these organs, highly specialized parenchymal cells
are frequent targets of HCMV infection, including hepatocytes in the liver
(Sinzger et al. 1999a), alveolar epithelial cells in the lung (Ng Bautista and
Sedmak 1995; Sinzger et al. 1995), and neuronal cells in retina and brain (Wiley
and Nelson 1988; Schmidbauer et al. 1989; Rummelt et al. 1994). In principle,
HCMV can thus cause extensive lesions because of its cytolytic nature, which
is, however, in most cases limited by a marked cellular immune response
(Sinzger and Jahn 1996).
Target Cells of HCMV in Cell Culture
An increasing number of cell culture models almost perfectly reflect the in vivo
situation concerning susceptibility of the various cell types. Again, lymphocytes
and granulocytes are among the few cell types that were not found to support
replication of HCMV in vitro, although they may still act as a passive vehicle for
HCMV transmission. On the contrary, the list of susceptible primary cell cultures
is long, including skin or lung fibroblasts, vascular smooth muscle cells
(Tumilowicz et al. 1985), retina pigment epithelial cells (Tugizov et al. 1996),
placental trophoblast cells (Halwachs-Baumann et al. 1998), hepatocytes (Sinzger
et al. 1999a), neuronal and glial brain cells (Poland et al. 1990), kidney epithelial
cells (Heieren et al. 1988), monocyte-derived macrophages (Ibanez et al. 1991;
Lathey and Spector 1991), monocyte-derived dendritic cells (Riegler et al. 2000),
and vascular endothelial cells (Ho et al. 1984; Waldman et al. 1989). All of these
primary cell types support the complete viral replication cycle, acquire a uniform
cytomegalic appearance during the late replication phase and are finally lysed
(Fig. 1b). In addition, limited replication can be achieved in a number of immortal-
ized cell lines such as glioblastoma cells, teratocarcinoma cell lines or monocytic
cell lines. However, some kind of differentiation is often necessary to render such
cell lines supportive of a complete replication cycle (Shelbourn et al. 1989; Ibanez
et al. 1991; Lathey and Spector 1991; Spiller et al. 1997; Sinclair and Sissons
