Biology Reference
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suggestive that resistance to CMV-induced disease requires a quantitative
response and that immune evasion functions of this virus can dilute a normal
protective response and foster persistence of this virus (Krmpotic et al. 2001;
Holtappels 2002). Because of the close evolutionary relationship between the
HCMV virus and its human host and the persistence of replicating virus in normal
individuals, it appears that viral functions contribute to the détente reached by
this virus and its host.
Natural History of Acute CMV Infections in the Normal Host
Human CMV infection is ubiquitous in the populations throughout the world
(Weller 1971a, 1971b; Stagno and Britt 2006). Serological evidence of past infection
ranges from nearly 100% in children and adults from undeveloped countries in
Africa, Asia and South America to less than 30% in adults in some areas of North
America and northern Europe. Acquisition of HCMV is age-related in both developed
and undeveloped countries. In well-developed areas of the world such as the US
and northern Europe, serologic reactivity to HCMV increases at an approximate
rate of 2% per year after adolescence, whereas in the developing world near universal
serologic reactivity can be documented by adolescence (Stagno et al. 1982a, 1983;
Stagno and Britt 2006). Consistent with the spread of HCMV in populations,
animal CMVs spread efficiently in laboratory colonies and CMV-free colonies of
experimental animals such as guinea pigs and rhesus macaques must be actively
managed by separation of infected from noninfected animals. Only limited infor-
mation is available on the epidemiology of CMVs in wild populations of nonhuman
primates, but a study has documented near universal seropositivity in at least one
free-ranging population of these animals (Swack and Hsiung 1982; Kessler et al.
1989; Vogel et al. 1994). Thus, the high incidence of RhCMV infection in rhesus
macaque colonies is more likely related to the natural spread of this virus than to
factors associated with captivity. Similarly, MCMV infection is commonplace in
wild mice captured in Australia and viruses isolated from wild mice quickly infect
laboratory mice when the two populations are housed together, regardless of the
preexisting infections in the laboratory animals (Gorman et al. 2006; Smith et al.
2006). Together, these data indicate that CMVs are readily transmitted within
populations through close contact and that increasing seroprevalence in human
populations indicates continued exposure to these viruses secondary to the endemic
and persistent nature of CMV infection within its animal host.
Children have been proposed to be a major source of CMV infections in human
populations. Documented routes of infection in children include perinatal exposure
to infectious genital secretions, breast milk ingestion, and exposure to other children
infected with HCMV (Stagno et al. 1980; Pass et al. 1987; Adler 1989, 1991;
Minamishima et al. 1994; Bale et al. 1996, 1999; de Mello et al. 1996; Vochem
et al. 1998; Hamprecht et al. 2001; Lawrence and Lawrence 2004; Willeitner 2004;
Doctor et al. 2005; Miron et al. 2005). Because HCMV infection at an early age is
