Biology Reference
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their host cell tropism and often induce variable cellular responses following infection
(Plachter et al. 1996; Fish et al. 1998; Sinzger et al. 1999b; Prichard et al. 2001;
Murphy et al. 2003). Experimental systems that permit efficient genetic manipulation
of CMV together with the promise of genomewide monitoring of gene expression of
CMVs will undoubtedly renew interest in the pathogenesis of infection with these
viruses and potentially identify previously unrecognized contributions of this large
DNA virus to human diseases (Zhu et al. 1998; Chambers et al. 1999; Hobom et al.
2000; Messerle et al. 2000; Simmen et al. 2001; Dunn et al. 2003; Yu et al. 2003;
Rupp et al. 2005; Streblow et al. 2007). This brief discussion will focus on the patho-
genesis of diseases associated with HCMV and attempt to integrate observations in
relevant animal models to current understanding of human disease.
The predictable occurrence of CMV end-organ disease in significantly immuno-
compromised hosts clearly demonstrates the importance of the immune system in
limiting virus replication and disease (Table 1). Although the risk of acute disease
following HCMV infection in allograft recipients is well recognized, our under-
standing of the key elements of immune control of this infection has been based
almost entirely on observations made in patients with significant and sometimes
global deficiencies in immune reactivity. Animal models, most notably murine and
Table 1
Clinical manifestations of HCMV infection
Population
Diseases associated
Diseases associated
with acute infection
with chronic infection
Immunocompetent
Asymptomatic infection,
Atherosclerotic vascular disease;
mononucleosis-like
inflammatory bowel disease,
illness
periodontal disease,
rheumatologic disorders
Immunocompromised
Asymptomatic (90%)
Hearing loss (5%-15%);
fetal and newborn
infections; 10% can have
neuron-developmental
infants (congenital
hepatitis, retinitis,
abnormalities
infection)
thrombocytopenia,
neurologic disease
Allograft recipients
Fever, decreased
Vascular disease
bone marrow function,
(transplant vasculopathy),
hepatitis, pneumonitis,
interstitial tubuloscleorsis
bacterial superinfections
(renal allografts); loss
of bile ducts (liver
allografts); chronic
graft rejection and
graft loss
Immunodeficiency
Gastrointestinal disease
Colitis reported in
syndromes (acquired
(esophagitis, colitis),
inherited immunodeficiencies
and inherited)
retinitis, encephalitis
Aged
Unknown
Immune senescence
with potential decrease
in immune responsiveness
