Biology Reference
In-Depth Information
infection or by passively transporting infectious particles as a vehicle. The latter
obviously applies for polymorphonuclear cells, which can take up virus particles
and express viral immediate early proteins but do not support the full replicative
cycle (Grefte et al. 1994). Even though these cells can not produce viral progeny,
they are still capable of transmitting the infection to other cell types, as evidenced
by frequent isolation of HCMV from polymorphonuclear cells of immunocom-
promised patients (Gerna et al. 1992), and this is most likely due to attachment
and partial localized fusion of cell membranes with subsequent transfer of
engulfed (sub)viral particles, as shown in the opposite direction for the transfer of
HCMV from endothelial cells to polymorphonuclear cells (Gerna et al. 2000). In
line with these hypotheses, (a) infectivity is predominantly found in the polymor-
phonuclear fraction of whole blood (Schafer et al. 2000), (b) detection of the viral
structural antigen pp65 (pUL83) in polymorphonuclear cells can be clinically
used as a marker of acute HCMV infection (The et al. 1990; Gerna
et al. 1991) and (c) removal of white blood cells from whole blood prior to trans-
fusion almost completely reduces the risk of HCMV transmission (Gilbert et al.
1989). Monocytes, although a minor target cell with regard to frequency, might
also contribute to hematogenous spread of HCMV, particularly as monocyte-
derived macrophages support the full replicative cycle (Ibanez et al. 1991; Lathey
and Spector 1991). It is tempting to assume a scenario where monocytes rolling
along the vascular endothelium take up infectious virus from productively
infected endothelial cells at one site of the body, differentiate upon transmigration
through an activated endothelial layer at a different site of the body (Waldman
et al. 1995), and release virus progeny into the corresponding organ after matura-
tion into tissue macrophages (Sinzger et al. 1996).
Apart from their role in acute HCMV infections, all susceptible cell types may in
principle also be sites of viral latency, although experimental data point to a particu-
lar role of hematopoietic cells in that context (Sinclair and Sissons 2006 see also the
chapters by M. Reeves and J. Sinclair, this volume). Taken together, the pathogenesis
of acute HCMV infections is greatly influenced by the broad target cell range of this
virus, with hematopoietic cells facilitating systemic spread, ubiquitous cell types
like fibroblasts and smooth muscle cells providing the platform for efficient prolif-
eration of the virus and epithelial cells contributing to interhost transmission.
Cell Biological Basis of HCMV Cell Tropism
The longstanding paradox between broad cell tropism of HCMV in vivo and a
restricted target cell range of the available virus strains in cell culture has been
resolved by the introduction of endothelial-propagated virus strains with a well-
preserved natural cell tropism. This enabled recent progress toward the definition
of viral genes governing interstrain differences in cell tropism and the first insights
into the underlying virus-host interactions.
