Differential expression of the coxsackievirus and adenovirus receptor regulates adenovirus infection of the placenta

The molecular mechanisms and pathologic significance of placental viral inf ections are poorly understood. We investigated factors that regulate placen tal infection by adenovirus, which is the most common viral pathogen identi fied in fetal samples from abnormal pregnancies (i.e., fetal growth restric tion, oligohydramnios, and nonimmune fetal hydrops). We also determined the pathologic significance of placental adenovirus infection. Northern hybrid ization, flow cytometry, and immunostaining revealed that placental express ion of the coxsackievirus and adenovirus receptor (CAR) varied with gestati onal age and trophoblast phenotype. The CAR was continuously expressed in i nvasive or extravillous trophoblast cells but not in villous trophoblast ce lls. We postulate that the villous syncytiotrophoblast, which does not expr ess CAR and is resistant to adenovirus infection, limits the transplacental transmission of viral pathogens, including adenovirus. Conversely, extravi llous trophoblast cells underwent apoptosis when infected by adenovirus in the presence of decidual lymphocytes (which simulated the maternal immune r esponse to viral infection). Thus, adenovirus infection and/or the maternal immune response to adenovirus infection induced the death of placental cel l types that expressed CAR. Consequently, we speculate that adenovirus infe ction of extravillous trophoblast cells may negatively impact the process o f placental invasion and predispose the mother and fetus to adverse reprodu ctive outcomes that result from placental dysfunction.