The human cytomegalovirus

Human cytomegalovirus (HCMV), a betaherpesvirus, represents the major infectious cause of birth defects, as well as an important pathogen for immunocompromised individuals. The viral nucleocapsid containing a linear double-stranded DNA of 230 kb is surrounded by a proteinaceous tegument, which is itself enclosed by a loosely applied lipid bilayer. Expression of the HCMV genome is controlled by a cascade of transcriptional events that leads to the synthesis of three categories of viral proteins designated as immediate-early, early, and late. Clinical manifestations can be seen following primary infection, reinfection, or reactivation. About 10% of infants are infected by the age of 6 months following transmission from their mothers via the placenta, during delivery, or by breastfeeding. HCMV is a significant post-allograft pathogen and contributes to graft loss independently from graft rejection. Histopathologic examination of necropsy tissues demonstrates that the virus enters via the epithelium of the upper alimentary, respiratory, or genitourinary tracts. Hematogenous spreading is typically followed by infection of ductal epithelial cells. Infections are kept under control by the immune system. However, total HCMV clearance is rarely achieved, and the viral genome remains at selected sites in a latent state. Virological and molecular detection of HCMV, as well as serological demonstration of a specific immune response, are used for diagnosis. Treatment of HCMV infections is difficult because there are few options. The presently available drugs produced a significant clinical improvement, but suffer from poor oral bioavailability, low potency, development of resistance in clinical practice, and dose-limiting toxicities. (C) 2003 Elsevier Science Inc. All rights reserved.