Human cytomegalovirus transmission and local immunity at the maternal-fetal interface

Human cytomegalovirus (HCMV) is the most common cause of congenital infection. Congenital HCMV infection affects an average of 0.64% live births worldwide and is associated with neurosensorial hearing loss, a wide range of neurodevelopmental disabilities, and placental insufficiency. Primary and (to a lesser extent) recurrent maternal infection, acquired by horizontal person-to-person transmission, can lead to vertical viral transmission to the fetus via the placenta. Our current knowledge of immune correlates of protection against congenital infection, and of prenatal disease markers is largely limited by the lack of relevant animal models for this human-specific virus. Hence, despite the immense health burden of congenital HCMV, no established preventive measures are currently available. There is an increasing need to better understand the mechanisms modulating the transmission and pathogenesis of congenital HCMV infection. Towards this goal, our studies in a unique ex vivo model of HCMV infection in native human placental tissues have revealed distinct patterns of infection, as well as innate immune response and damage pathways activated by HCMV at the maternal-fetal interface. In my talk, I will also present new findings on the very initial events of infection and tissue-response during HCMV mucosal-site entry into the human host. Our results present new approaches towards developing new therapies and vaccines against HCMV infections. The impact of these findings will be discussed in this presentation.