Biology Reference
In-Depth Information
2006). While in vivo analyses were apt to descriptively identify the cell types
infected by HCMV in its natural host, cell culture models made it possible to
address quantitative aspects regarding susceptibility and productivity, thus reveal-
ing striking differences between cells of different origin: skin or lung fibroblast
have always been the standard cell type for isolation and propagation of HCMV
from patient samples and are still the most efficient producer cell line irrespective
of the virus strain (Mocarski et al. 2006). For certain HCMV strains, vascular
endothelial cells are also sufficiently susceptible and productive to allow long-
term propagation of certain virus strains by passaging cell-free supernatants of
infected cultures (Digel and Sinzger 2006). Other cell cultures, e.g., monocyte-
derived macrophages, are low-level productive (Sinzger et al. 2006) and hardly
release sufficient amounts of infectious progeny to maintain the virus during
repeated passaging of cell-free supernatant on the respective cell type.
Cell Tropism
Along with the description of quantitative differences regarding susceptibility and
productivity, different definitions of cell tropism may be applied to describe differ-
ent aspects of HCMV-host cell interactions. In a broader sense, cell tropism refers
to the simple fact that cells can be entered by the virus and will subsequently
express viral genes. More functional definitions of cell tropism may take into
account whether the infection is effective. From a biologist's point of view, cell
tropism might define those target cells in which the virus can successfully repro-
duce. From a pathologists view, cell tropism might define those target cells that are
damaged by the virus regarding cell survival and/or specific cellular functions.
Thus, even though HCMV infection of polymorphonuclear cells is abortive
(Grefte et al. 1994), these cells can obviously contribute to hematogenous spread
via the blood stream by carrying internalized virions (Gerna et al. 2000).
Similarly, even though generation of viral progeny appears to be rather ineffec-
tive in monocytes/macrophages (Sinzger et al. 2006), this might suffice to start
infection in an organ after transmigration through the vascular endothelium.
Likewise, low-level production in placental trophoblast (Halwachs-Baumann et al.
1998), even though insufficient for long-term propagation of HCMV in trophoblast
cultures, can contribute critically to intrauterine infection of the fetus (see also
the chapter by L. Pereira and E. Maidji, this volume). Skin fibroblasts, lung
fibroblasts and human umbilical vein endothelial cells are suitable for long-term
propagation of clinical HCMV isolates, i.e., these cells have a reproductive
index greater than 1. During the initial passages when isolates grow strictly cell-
associated (Yamane et al. 1983), this would result in an increase of the fraction
of infected cells within the culture. After adaptation to a cell-free infection
mode, a reproductive index of greater than 1 would mean that progeny produc-
tion exceeds virus input in the respective cell culture. The cell type used for
