Lenore Pereira
University of California San Francisco, USA
Title: Epithelial cells of the amniotic membrane sustain persistent cytomegalovirus infection in the human placenta
Biography
Biography: Lenore Pereira
Abstract
Human cytomegalovirus (HCMV) is the leading viral cause of birth defects, including neurological deficits, impaired hearing and vision loss. We previously reported that epithelial cells in amniotic membranes of placentas from newborns with intrauterine growth restriction and underlying congenital infection contain HCMV proteins in cytoplasmic vesicles. Here we immunostained amniotic membranes from diagnosed symptomatic congenital infection and preterm deliveries and detected viral proteins and aberrant epithelial cell morphology in cases of virus transmission. Primary amniotic epithelial cells (AmEpC) infected with pathogenic viral strainsdysregulated stem cell proteins, and viral replication was gestational age dependent. In contrast to highly differentiated retinal pigment epithelial cells, infected AmEpC failed to make intact viral assembly compartments and instead formed diffusely localized multivesicular bodies, proliferated and survived for months releasing progeny without plaque formation. Explants of amniochorionic membranes infected ex vivo upregulated IFN-ï¢ in surrounding epithelial cells. Infected AmEpCs produced IL-6 and upregulated the anti-apoptotic proteins survivin and Bcl-xL by mechanisms dependent and independent of the activated signal transducer and activator of transcription 3. Both survivin and Bcl-xL were expressed by control and infected amniotic membranes in utero, suggesting an opportune environment to sustain persistent infection. Interventions that target signaling pathways contributing to HCMV persistence in AmEpC could reduce the viral load and inflammation in the fetal compartment and improve outcome.