The overall objective of this proposal is to investigate the natural history of sexually acquired cytomegalovirus (CMV) infection. Using both prevalence surveys and prospective cohort studies we will systematically analyze and correlate CMV infection with sexual practices, level of sexual activity, changes in sex partners and other correlates of sexual activity. Cohort studies to assess the frequency of acquisition of disease, anatomic sites and duration of excretion of CMV from genitourinary sites in clients of sexually transmitted disease clinics, university health center populations, and adolescents attending medical clinics will be performed. Sex partners of persons with and without CMV infection will be followed to evaluate the frequency of CMV transmission from contact with persons with persistent or chronic CMV infection. Restriction enzyme typing will be utilized to compare isolates from sex partners in order to distinguish endogenous relapse with exogenous reinfection. Both local and systemic host immune responses to specific viral polypeptides using radioimmunoprecipitation and Western blot analysis will be performed. In situ hybridization techniques for the detection of CMV DNA will be performed in order to assess the sites of CMV in the genitourinary tract. Comparison of conventional isolation methods, detection of CMV antigen with monoclonal antibodies and CMV DNA by Southern blotting and in situ hybridization methods with clinical expression and transmission of disease will further our understanding of the natural history and persistence of CMV infection of the genitourinary tract.