Lenore Pereira
University of California San Francisco, USA
Title: Prototype and nicaraguan strains of zika virus infect primary human placental cells expressing Axl, Tyro3 and TIM1 receptors at the uterine placental interface, modulated by individual donors
Biography
Biography: Lenore Pereira
Abstract
The Zika epidemic that began in Braziland has spread throughout the Americas has beenreported as definitively linked to severe birth defects – microcephaly, miscarriage and stillbirth.Detection of ZIKV RNA in the placenta and fetus and frequent intrauterine growth restriction suggestsinfection of the placenta leading to pathology.Our studies in primary cells from 14 placentas reveal that prototype and recently iso¬lated Nicaraguan ZIKV 2016 strains infect cells that express Axl, Tyro3 and TIM1 tyrosine kinase receptors, which modulate innate immune responses and mediate infection by ZIKV and the closely related dengue virus (DENV) infection in skin. Infected placental cells, including fetal-derivedamniotic epithelial cells (AmEpC), trophoblast progenitor cells (TBPC),placental fibroblasts (HPF),umbilical veinendothelial cells (HUVEC)and differentiating cytotrophoblasts(CTBs) showed cytopathic effects, expressed ZIKV envelope and non¬structural NS3 proteins, and titers of infectious progeny depended on cell type, receptors expressed,individual donors and gestational age.Indicative of infection route, the decidua (decidual cells, invasive CTBs), chorionic villi (HPF, Hofbauer cells, blood vessels) and amniochorionicmembranes (AmEpC,TBPC) expressed the receptors. Nonetheless, differential expression was foundin 26 biopsy specimens, in particular TIM1 was detected throughout pregnancy, but Axl was absent in late gestation. In summary, the results suggest that ZIKV could infect the pregnantuterus and spread to the placenta, fetus and amniochorionic membranes. The models of placental infection we have developed can be used to understand molecular mechanisms of ZIKV infection and assess the therapeutic potential of antibodies and small molecule inhibitors to block infection in the placental-fetal unit.