Joining the dots: maternal cytomegalovirus, HIV and the placenta.

Elucidating how HIV and cytomegalovirus (CMV) co-infection in pregnancy disrupts immune homeostasis at the maternal-fetal interface can provide a foundation for developing intervention strategies to improve infant and maternal health. Of importance is the identification of infant immune dysregulation, especially in HIV-exposed uninfected newborns (HEU). Although vertical transmission of HIV has been substantially mitigated by antiretroviral treatment, the incidence of adverse birth outcomes remains significantly higher in these infants than in those born to mothers without HIV. We hypothesize that the immune status of mothers during pregnancy impacts upon the placenta, in turn affecting infant immunity. We explore this hypothesis by examining data from key studies and clinical cohorts, aiming to 'join the dots' to form a body of knowledge to catalyse development of more comprehensive studies. Our narrative represents a thought piece incorporating events around HIV and CMV during the antenatal period, the impact of maternal immunity and immune events in the placenta, and how these factors produce a 'knock-on' effect on infant immune ontogeny and susceptibility to poor health. We introduce the concept of vertical transmission of inflammation, where in the absence of viral transmission, the effects of a maternal inflammatory milieu could profoundly impact birth and infant outcomes via placental dysfunction.This article is part of the discussion meeting issue 'The indirect effects of cytomegalovirus infection: mechanisms and consequences'.