Cellular determinants of parvovirus B19 infection in the human placenta

Abstract

Parvovirus B19 (B19V) is a prevalent human pathogen that can cross the placenta by a mechanism that remains unknown, posing a risk of severe fetal complications, particularly during the first trimester of pregnancy. We investigated the expression of B19V-specific receptors in the three trophoblast cell types, cytotrophoblasts (CTBs), syncytiotrophoblasts (STBs), and extravillous trophoblasts (EVTs), and assessed their susceptibility to infection. VP1uR, the erythroid-specific receptor that mediates viral uptake and infection in erythroid progenitor cells, is expressed in CTBs and STBs, but not in EVTs. Globoside, a glycosphingolipid that is essential for the escape of the virus from endosomes, is also expressed in these cells, except for choriocarcinoma-derived CTBs. In the latter, the absence of globoside can be overcome by promoting endosomal leakage with polyethyleneimine. While erythropoietin receptor (EpoR) signaling is associated with the strict erythroid tropism of B19V, it is not required for infection in trophoblasts. Transfection experiments revealed that highly proliferative first-trimester CTBs are more permissive to B19V infection than the low-proliferative CTBs from term placenta. These findings demonstrate that B19V targets and infects specific trophoblast cells, where viral entry and replication are collectively mediated by VP1uR, globoside, and high cellular proliferative activity, but are independent of EpoR signaling. HighlightsO_LITrophoblasts express the specific receptors necessary for B19V entry. C_LIO_LISusceptibility and permissiveness to B19V vary by trophoblast subtype and gestational age. C_LIO_LIHighly proliferative first-trimester cytotrophoblasts show increased permissiveness to B19V. C_LIO_LIB19V infection in trophoblasts depends on globoside but is independent of EpoR signaling. C_LI