Congenital cytomegalovirus infection: identification of factors determining vertical transmission and clinical outcome of infected neonates

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Congenital infection with cytomegalovirus (CMV) in newborns is the most frequent infectious cause of permanent disabilities. Currently, there is no established therapy available to prevent neonatal CMV disease. Although recognized as a global clinical problem, prenatal factors determining vertical virus transmission from mother to foetus are still unknown. Moreover, it remains poorly understood why most infected neonates remain asymptomatic whereas some show moderate or severe disease symptoms.Here, we aim to investigate factors that could increase the risk of prenatal CMV-infection and severity of neonatal CMV disease. Utilizing human samples obtained from the PRINCE cohort (Service Project S1) in combination with a mouse model for congenital CMV infection we will determine the role of prenatal challenges, the anti-CMV T cell response of mother and child, and viral pathogenicity factors. Using an established CMV mouse model, we will clarify if maternal stress and medication intake during pregnancy - challenges which are potentially avoidable – render the offspring more prone to develop a severe course of early life CMV infection. In depth characterisation of maternal and neonatal antigen-specific T cells will define their role in control of CMV infection during the early life phase. Finally, in parallel to the host immune response we will investigate the pathogen itself to identify viral genetic factors that determine its pathogenicity and likelihood of vertical transmission. In summary, we intend to answer pending questions of CMV infection biology at the interface of reproduction, paediatrics, immunology, and virology that could lay the basis for new diagnostic or therapeutic approaches.