Biology Reference
In-Depth Information
and m143) that blunt PKR responses to dsRNA, and deletion of these viral genes
cripples replication virus in vivo (Valchanova et al. 2006). Thus, HCMV encodes a
number of viral functions to prevent both intrinsic and innate cellular responses to
infection, presumably to facilitate virus replication and generation of progeny virions.
Finally, it should be noted that the presence of infiltrating lymphocytes and other
mononuclear cells and elevated levels of inflammatory cytokines in HCMV-
infected tissue also raise the possibility that host-derived immune effector functions
contribute to disease manifestations associated with acute infection. In support of
this possibility is the observation that children infected as fetuses, newborns or
during infancy excrete virus for prolonged periods of time, in many cases several
years, and yet do not exhibit clinically observable organ dysfunction (Stagno and
Britt 2006). Thus, viral replication apparently does not represent the sole determinant
of disease in the normal host.
Resolution of acute infection in normal individuals is associated with persistent
immunological reactivity for HCMV that is characterized by a high frequency of
HCMV-specific CD4
+
and CD8
+
T lymphocytes and stable levels of antiviral
antibodies. Even in the face of persistent immunological reactivity specific for
HCMV, normal individuals, as noted previously, can be reinfected with heterologous
strains of virus. Whether the persistently elevated levels of anti-HCMV antibodies
and HCMV-specific T lymphocytes detected in some individuals result from frequent
reinfection is unknown. Furthermore, immune individuals periodically excrete
infectious virus and the infected host remains the main source of community exposure
for the uninfected individual.
Virus has been demonstrated in a variety of cell types in normal individuals with
acute infections, including epithelium, hepatocytes, smooth muscle cells, endothelial
cells, circulating mononuclear cells, macrophages, astrocytes and dermal fibroblasts
(Tumilowicz et al. 1985; Sinzger et al. 1995, 1996, 1999a; Ricotta et al. 2001).
Similar findings have been described in experimental animals. Virus persists in a
number of tissues following resolution of an acute infection and may persist either
as a chronic productive infection or as a latent infection. In experimental rodents,
virus can be consistently recovered from the salivary gland. Virus has also been
recovered from latently infected blood monocytes following culture in supernatant
fluids from cultures of lymphocytes undergoing an allogenic reaction (Soderberg-
Naucler et al. 1997). This finding was an extension of early studies in mice infected
with murine CMV and demonstrated that a latent infection could contribute to
CMV persistence (Jordan and Mar 1982). In addition, the finding that latent HCMV
present in mononuclear cells could be reactivated by an ongoing allogenic reaction
provided an explanation for the role of the transplanted organ as a source of CMV
reactivation in patients undergoing allotransplantation (Gnann et al. 1988;
Soderberg-Naucler et al. 1997). It remains unclear if persistence of CMV infection
in humans can be best described as a chronic productive infection in sequestered
sites or as a true latent infection with periodic reactivations, or more likely by both
mechanisms. Most investigators would favor the description of CMV persistence as
a chronic persistent replication. In the postpartum period, it appears that a previ-
ously quiescent infection can be reactivated in both genital tract and in the secretory
