Biology Reference
In-Depth Information
The tropism for endothelial cells, macrophages and dendritic cells varies greatly
among different HCMV strains, mostly dependent on alterations within the UL128-
131 gene locus. In line with the classification of the respective proteins as structural
components of the viral envelope, interstrain differences concerning the infectivity
in endothelial cells and macrophages are regulated on the level of viral entry.
Target Cells of HCMV Infection
The question of which cell types in which tissues are targets of HCMV infection
derives its relevance from the trivial fact that a virus can only live inside its host
cell. The biology of a virus and, even more, its pathogenic effects within the
infected organism are therefore inevitably linked to the spectrum of susceptible
cell types.
Target Cells of HCMV In Vivo
Generally speaking, HCMV is tightly restricted to humans on the host level, but
within the human host it can spread to virtually any tissue due to an exceptionally
broad range of target cell types. In fact, it is easier to list the cell types that do not
support HCMV replication: despite early reports about some degree of IE gene
expression in lymphocytes in cell culture (Rice et al. 1984), we have not found
IE antigens in cells of lymphoid origin during extensive immunohistochemical
analyses of various organ tissues from acutely infected patients (Sinzger et al.
1995). A similar block of viral replication occurs in polymorphonuclear leuko-
cytes. While these cells can take up virus particles and express IE antigens to
some extent, transcripts and proteins of the early and late phase of viral replica-
tion are not found (Grefte et al. 1994; Sinzger et al. 1996). These two exceptions
are faced by a long list of susceptible cell types, including various cells of
ectodermal, mesodermal and endodermal origin. Most prominent examples are
epithelial cells of glands and mucosal tissues, connective tissue cells in various
organs, smooth muscle cells predominantly in the gastrointestinal tract and
vascular endothelial cells (Sinzger et al. 1993; Ng Bautista and Sedmak 1995;
Sinzger et al. 1995). Due to the strict host specificity, HCMV infection cannot be
studied experimentally in animals, and in vivo data are hence only available from
the analysis of diagnostic patient samples or autopsy materials. Dynamic aspects
of viral replication and spread have therefore only been addressable within the
blood compartment (Emery et al. 1999). Nevertheless, multiple circumstantial
evidence strongly suggests successful viral replication in the above-mentioned
cell types: Numerous capsids in the nucleus of infected cells as detected by
electron microscopy unequivocally represent late-stage infection (Donnellan
et al. 1966; Martin and Kurtz 1966; Kasnic et al. 1982; Balazs 1984; Francis
