Molecular pathogenesis of human cytomegalovirus infection

Despite progress in diagnosis and treatment of human cytomegalovirus (CMV) infection, we do not understand why, in hosts with comparable levels of immunosuppression, some CMV infections result in symptomatic CMV disease while others are limited to asymptomatic virus shedding with no discernible clinical consequences. CMV viral detection and quantification are useful for identifying those at highest risk, but do not consistently predict clinical outcome. Factors such as host genotype and immune response are active areas of research. However, the importance of CMV strain variability, recognized since 1976, is now receiving attention. Advances in technology that allow the rapid sequencing of viral DNA for purposes of strain characterization have fueled the renewed interest. The focus of this review will be to summarize our evolving knowledge of CMV strain variability and to document where possible a potential relationship to strain virulence. Studies with the UL55 (gB) envelope glycoprotein will be emphasized because of the ability to clearly identify naturally occurring variants, as well as the increasing number of reports that there are differences in biological activities that may contribute to virulence.