Biology Reference
In-Depth Information
Epithelial Cells
Epithelial cells are a major target of HCMV infection (Sinzger et al. 1995) and can
therefore be assumed to play an important role during host-to-host transmission as
they line all external body surfaces. Most likely, HCMV enters a new host by
infection of mucosal epithelium. For example, HCMV newborns and infants can
be infected by breast milk of a seropositive mother, a highly efficient transmission
route which accounts for the majority of HCMV transmissions during early child-
hood (Stagno and Cloud 1994). More than 95% of seropositive breastfeeding
women reactivate HCMV locally, shed cell-free infectivity into the milk, and
30%-40% of them will transmit HCMV to their children (Hamprecht et al. 2001).
The infants' mucosal surfaces throughout the gastrointestinal tract are exposed
during feeding, and epithelial cells in all parts of the gastrointestinal tract are sus-
ceptible and obviously support productive infection. They are the most likely can-
didates for primary replication of incoming HCMV. However, as these first steps
of infection are hardly ever recognized, there are no data available for a direct
proof of these considerations. Alternatively, similar to HIV, dendritic cells could
also contribute to entry via mucosal surfaces.
More direct data are available supporting a role of epithelial cells in shedding
HCMV into body fluids. During acute productive infection, late-stage-infected
epithelial cells have been detected in salivary glands, kidney and various parts of
the gastrointestinal tract (Variend and Pearse 1986; Sinzger et al. 1995; Bissinger
et al. 2002). Undoubtedly, these cells are a source of infectivity detected within
saliva, urine and stool and may thus contribute to HCMV transmission via these
excretions.
Dendritic Cells
Because of their complex biology, dendritic cells (DCs) may play various roles in
the pathogenesis of HCMV infections, resulting in proviral as well as antiviral
effects. Immature DCs are resident in virtually all mucosal and epidermal surfaces
of the body, controlling for the invasion of foreign organisms. They are well
equipped for highly efficient endocytic uptake of material from their environment,
e.g., pathogens or remnants from apoptotic cells. Uptake of infectious HCMV into
DCs can result in viral replication and release of viral progeny (Riegler et al.
2000). On the other hand, endocytic uptake of HCMV may lead to processing of
viral proteins and presentation of viral epitopes by MHC class I and II molecules.
This is counteracted to some extent by HCMV-induced downregulation of several
immune-stimulatory surface molecules including MHC class I and II (Grigoleit
et al. 2002; Moutaftsi et al. 2002; Hertel et al. 2003). As a consequence, HCMV-
infection decreases the immune-stimulatory capacity of DCs (Grigoleit et al. 2002;
Moutaftsi et al. 2002; Hertel et al. 2003). For immature DCs, antigen uptake is a
