Biology Reference
In-Depth Information
in which virus gene expression and virus replication are closely related to host
inflammatory responses and likely promote host inflammatory responses leading to
tissue damage.
Diseases Associated with Chronic Infection
Although the concept that chronic HCMV infection could be associated with
identifiable disease syndromes seems likely because of the persistent nature of
HCMV infection, definitive evidence linking HCMV with chronic disease is
limited. Several characteristics of this virus-host relationship has made definitive
studies difficult. First, the virus is ubiquitous in the population, with the incidence of
infection exceeding 80% in some populations, often higher than the incidence
of common chronic diseases. The high prevalence of infection has made epidemi-
ological studies of disease association nearly impossible because of the need to
study large numbers of patients to obtain sufficient statistical power. In addition,
many studies have flaws in their design such as differing disease classifications,
confounders such as race and other independent risk factors of disease, and
differences in classifications of HCMV infection. Secondly, pathogenic mecha-
nisms other than lytic virus replication are not well understood and animal model
systems that may permit more informative studies of potential mechanisms have
only recently been described. Moreover, the presence of viral nucleic acid or
virus-encoded proteins in a tissue does not necessarily reflect disease association
and may merely represent virus present as a passenger in a circulating mononu-
clear cells or tissue macrophages. Recent evidence has also indicated that viral
strains from different patients may differ genetically and in their cellular tropism,
thus offering another layer of complexity in the lytic and nonlytic effects of
HCMV infections that could contribute to chronic disease. Finally, studies in
animal models have demonstrated that the pattern of viral gene expression varies
within the host depending on the site of infection (Streblow et al. 2007). This
latter finding provides an especially strong argument for the bidirectional rela-
tionship between CMV and the host and suggests that merely detecting viral
nucleic acids or viral protein expression will provide only a limited understanding
of the contribution of this virus to organ-specific chronic diseases. Even with
these limitations in mind, a myriad of studies from allograft transplant recipients
and normal hosts have presented a strong case for HCMV as a co-factor in
chronic inflammatory processes, particularly those resulting in vascular disease.
Studies in experimental animals have also revealed several plausible mechanisms
for a potential contribution of HCMV to chronic vascular disease. Lastly, HCMV
has been suggested to be a co-factor in some human malignancies based on
epidemiological studies in populations with a high incidence of HCMV infection
(Huang et al. 1984; Shen et al. 1993; Han et al. 1997). More recent studies suggest
that HCMV could also have a potential role in specific human malignancies,
perhaps serving as a promoter for tumor invasion or proliferation. Several
