MOLECULAR EPIDEMIOLOGY OF PRIMARY CMV INFECTION

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DESCRIPTION (provided by applicant): Dr. Ravit Boger is an assistant professor, division of pediatric infectious diseases at Johns Hopkins. In recent years, she worked with her mentors Dr. Hayward and Dr. Pass on CMV strain variation. Through this K08 award, she will conduct translational research to determine the molecular epidemiology of primary CMV infection in healthy adults, and gain expertise in molecular epidemiology and virology, advanced skills in genome sequencing, real-time PCR, and the responsible conduct of research. Molecular techniques have detected numerous CMV strains in the population. Primary human CMV infection is traditionally believed to be caused by a single strain, and isolation of multiple strains has been considered proof of re-infection. While specific populations (transplant recipients, AIDS patients, children in day care, etc.) may over time be re-infected with multiple CMV strains, no previous studies have determined whether initial CMV infection in healthy subjects involves multiple strains. Previously, we identified multiple CMV strains from tissues of CMV-induced fetal demise, yet only a single strain was identified from cultured isolates of CMV-infected live infants. It is unclear whether this difference has clinical significance or is related to direct sequencing from tissue as opposed to sequencing after selection of preferential isolates in culture. This application aims to characterize strain heterogeneity during primary CMV infection in a cohort of healthy women who participated in a randomized double-blind gB vaccine trial and who seroconverted during follow up. Dr. Boger will analyze hypervariable CMV genes from serial samples of original body fluids and cultured isolates that have been obtained from these individuals during primary CMV infection and 6-24 months afterwards. She will also determine whether vaccine-induced immunity affects the acquisition of strains over time, and whether specific genotypes are associated with viral load in various body fluids. This study will help understand the extent to which strain diversity can be used as evidence of re-infection and how natural CMV infection leads to broad immunity to the virus. This work is relevant to public health since strain variation may be responsible for increased virulence of some infections and because the phenomenon of strain variation may impact on the development of effective vaccine aimed at prevention of congenital CMV infection.