Biology Reference
In-Depth Information
syndromes associated with acute infection. End organ disease secondary to unchecked
virus replication can be observed in infants infected in utero, allograft recipients receiv-
ing potent immunosuppressive agents, and patients with HIV infections that exhibit
a loss of adaptive immune function. In contrast, diseases associated with chronic or
persistent infections appear in normal individuals and in the allografts of the transplant
recipient. The manifestations of these infections appear related to chronic inflamma-
tion, but it is unclear if poorly controlled virus replication is necessary for the different
phenotypic expressions of disease that are reported in these patients. Although the
relationship between HCMV infection and chronic allograft rejection is well known,
the mechanisms that account for the role of this virus in graft loss are not well under-
stood. However, the capacity of this virus to persist in the midst of intense inflammation
suggests that its persistence could serve as a trigger for the induction of host-vs-graft
responses or alternatively host responses to HCMV could contribute to the inflamma-
tory milieu characteristic of chronic allograft rejection.
Introduction
Cytomegaloviruses are readily transmissible beta-herpesviruses that establish persist-
ent infections for the life of the host. CMVs have been isolated from almost all mam-
malian species that have been studied, including commonly used experimental
laboratory animals. Several lines of evidence argue that CMVs co-evolved with their
natural hosts (Britt et al. 2005). These include the finding of functional host cell genes
incorporated into the viral genome, the near universal lack of clinically significant
disease following primary infection of the natural host, and a highly restricted tropism
for the homologous host that appears to be linked to blocks of genes specific for each
cytomegalovirus (Britt et al. 2005). This later biological property of CMVs has lim-
ited the use of experimental animals to precisely model human disease syndromes.
As a result, considerable efforts have been made to define the pathogenesis of human
CMV (HCMV) infections by observational studies. Recapitulation of all aspects of
HCMV infection has been impossible to achieve in experimental animal models, but
important insights into general mechanisms of virus persistence and immune control
of acute and chronic viral infections have been gained through the study of rodent and
more recently, rhesus macaque CMV infections.
Well-recognized disease syndromes follow acute infection with CMV and after
reactivation of latent infections in both immunocompromised human and animal
hosts; however, chronic persistent infections with CMV and possibly chronic abortive
infections with restricted viral gene expression have also been proposed to explain
less recognizable disease syndromes associated with these viruses. Several hurdles
continue to plague experimental study of chronic diseases associated with CMV,
including the complex organization and regulation of viral gene expression and more
recently the realization that commonly used laboratory virus strains of HCMV and
recent clinical isolates differ not only in their overall genetic composition but also
