Manifestations of Human Cytomegalovirus Infection: Proposed Mechanisms of Acute and Chronic Disease
Infections with human cytomegalovirus (HCMV) are a major cause of morbidity and mortality in humans with acquired or developmental deficits in innate and adaptive immunity. In the normal immunocompetent host, symptoms rarely accompany acute infections, al
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Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Natural History of Acute CMV Infections in the Normal Host . . . . . . . . . . . . . . . . . . . . . . . Natural History of Acute CMV Infection in the Immunocompromised Host . . . . . . . . . . . . Congenital Infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Allograft Recipients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Patients with AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diseases Associated with Chronic Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chronic Vascular Disease in the Normal Host. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chronic Disease in the Transplanted Allograft . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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Abstract Infections with human cytomegalovirus (HCMV) are a major cause of morbidity and mortality in humans with acquired or developmental deficits in innate and adaptive immunity. In the normal immunocompetent host, symptoms rarely accompany acute infections, although prolonged virus shedding is frequent. Virus persistence is established in all infected individuals and appears to be maintained by both a chronic productive infections as well as latency with restricted viral gene expression. The contributions of the each of these mechanisms to the persistence of this virus in the individual is unknown but frequent virus shedding into the saliva and genitourinary tract likely accounts for the near universal incidence of infection in most populations in the world. The pathogenesis of disease associated with acute HCMV infection is most readily attributable to lytic virus replication and end organ damage either secondary to virus replication and cell death or from host immunological responses that target virus-infected cells. Antiviral agents limit the severity of disease associated with acute HCMV infections, suggesting a requirement for virus replication in clinical
W. Britt Departments of Pediatrics, Microbiology, and Neurobiology, University of Alabama School of Medicine, Childrens Hospital, Harbor Bldg. 104, 1600 7th Ave. SouthBirmingham, AL 35233, USA [email protected]
T.E. Shenk and M.F. Stinski (eds.), Human Cytomegalovirus. Current Topics in Microbiology and Immunology 325. © Springer-Verlag Berlin Heidelberg 2008
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syndromes associated with acute infection. End organ disease secondary to unchecked virus replication can be observed in infants infected in utero, allograft recipients receiving potent immunosuppressive agents, and patients with HIV i
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