Biology Reference
In-Depth Information
propagation of an isolate has an effect on the cell tropism of the resulting HCMV
strain. Apparently, long-term propagation in fibroblasts selects for HCMV
strains with low endothelial cell tropism, whereas long-term propagation in
endothelial cells maintains the broader cell tropism characteristic for recent
clinical HCMV isolates (Waldman et al. 1991; Sinzger et al. 1999b). Whether
propagation in other cell types such as smooth muscle cells or macrophages
would also results in a restricted cell tropism has not been tested. Likewise, it is
unknown whether an adaptation of HCMV to certain cell types also takes place
during natural infection in vivo, i.e., whether tropism variants of HCMV exist
within one patient. At present, the assumption of different cell tropism variants
in different organ tissues is still speculative, but first hints in that direction come
from reports on a strictly localized reactivation of HCMV, e.g., in the lactating
breast (Hamprecht et al. 2003). Apart from viral determinants, a tissue-specific
immune control might also contribute to differences in the apparent organ
tropism of HCMV replication, similar to the apparent tropism of MCMV for the
salivary gland (Jonjic et al. 1989). Experimental data from murine cytomegalo-
virus indicate that under the complex in vivo conditions the apparent cell
tropism can be further modified by the microenvironment within a certain tissue.
For example, proapoptotic stimuli from surrounding immune cells can limit
infection in an otherwise susceptible cell type (Patrone et al. 2003), and this
proapoptotic effect might even occur in a cell type-specific manner. For a refined
understanding of HCMV's in vivo cell tropism, future work should therefore
take into account how the complex organ-typical interactions might influence
the susceptibility of target cells for HCMV infection, e.g., by analyzing complex
organ tissue cultures (Reinhardt et al. 2003).
In conclusion, the strict host tropism of HCMV is contrasted by a remarkably
broad cell tropism within its host, with epithelial cells, endothelial cells, fibroblasts
and smooth muscle cells being the predominant targets for virus replication. The
discrepancy between in vivo findings and cell culture data has diminished with the
introduction of more recent HCMV strains and their application in various primary
cell cultures. Since the basic cell culture tools reflecting the in vivo cell tropism of
HCMV are now available, the analysis of compound cell culture systems represent-
ing the complex composition of organ tissues can be targeted in the future.
Pathogenetic Role of Selected Cell Types
The broad target cell range provides the basis for a highly complex interaction
between HCMV and the human host, which can be adapted to many different sit-
uations during their lifelong relationship. It should always be kept in mind that
HCMV can successfully enter its host, spread within the body, establish latency,
reactivate frequently throughout life and be transmitted to other individuals
mostly without ever causing clinically apparent disease (for aspects of latency,
see the chapters by M. Reeves and J. Sinclair, this volume and M.J. Reddehase
