Biology Reference
In-Depth Information
epithelium of the breast (Pass et al. 1982; Hamprecht et al. 2001; Stagno and Britt
2006). In fact, reactivation of CMV in the breast epithelium and excretion into
breast milk is almost universal in previously infected women during the postpartum
period (Stagno et al. 1980; Stagno and Britt 2006). Finally, Reddehase and
colleagues carefully demonstrated in the murine model of CMV infection that true
latency existed in the lungs of previously infected animals and that following loss
of immune control, productive infection could be demonstrated (Kurz et al. 1999).
Whether active immune surveillance contributes to the establishment or maintenance
of CMV latency in humans is unknown.
Natural History of Acute CMV Infection
in the Immunocompromised Host
Exaggerated end-organ disease in the immunocompromised host has offered a
glimpse of the pathogenic potential of CMVs, yet extensive disease in the setting
of an absent or depressed immune system obviously does not reflect the phenotype
of this virus in the immunologically normal host. In fact, one could argue that
CMVs have evolved to be nonpathogenic in their hosts to ensure persistence and
spread in the population. Prior to the HIV pandemic, widespread multiorgan
disease had been described consistently in only one naturally acquired infection:
infants with congenital HCMV infection. Thus, in the context of the normal non-
immunocompromised host, the pathogenic potential of CMVs may be restricted to
those of chronic infection and not to the more recognizable disease manifestations
that are seen in patients with deficits in immune responsiveness. Nevertheless, the
manifestations of acute HCMV infection remain of considerable medical impor-
tance and unraveling its pathogenesis remains an important goal of current
research. HCMV has been associated with disease in three groups of immunocom-
promised hosts: (a) fetuses presumably secondary to immunological immaturity,
(b) allograft recipients secondary to cytotoxic antirejection agents and in some
cases graft-vs-host disease, and (c) HIV infection with loss of CD4
+
lymphocytes
and the resulting loss of adaptive immune responses (Table 1). Less commonly,
CMV disease has been reported in patients undergoing cytotoxic chemotherapy or
prolonged therapy with corticosteroids (Stagno and Britt 2006). An interesting
association of invasive CMV disease has been recently described in patients
undergoing anti-TNF antibody therapy of rheumatologic diseases (Haerter et al.
2004; Mizuta and Schuster 2005; Kohara and Blum 2006). Diseases in these
patients ranged from hepatitis, retinitis, and enteritis. Descriptions of intestinal
disease associated with CMV infection in older patients with inherited immunode-
ficiencies have also been reported (Raeiszadeh et al. 2007). Finally, the role of
HCMV in immune senescence in the aged population secondary to the phenomena
of memory inflation of the T lymphocyte response to this virus remains an area of
active investigation.
