# Cellular determinants of parvovirus B19 susceptibility in the human placenta

## TL;DR

This study identifies which placental cells are susceptible to parvovirus B19 infection and how the virus enters and replicates in these cells during early pregnancy.

## Contribution

The study reveals that B19V can infect trophoblast cells via VP1uR and globoside, independent of erythropoietin signaling.

## Key findings

- VP1uR and globoside mediate B19V infection in cytotrophoblasts and syncytiotrophoblasts.
- Highly proliferative first-trimester cytotrophoblasts are more susceptible to B19V infection.
- Erythropoietin receptor signaling is not required for B19V infection in trophoblasts.

## 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 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 susceptible to B19V infection than the low-proliferative CTBs from term placenta. These findings demonstrate that B19V targets 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.

Parvovirus B19 is a common human pathogen that can cross the placenta and infect the fetus, though the mechanism remains unknown. Here, we demonstrate that specific trophoblast populations at the maternal-fetal interface create conditions that enable infection. Viral entry and replication depend on specific receptors expressed in the syncytiotrophoblasts and cytotrophoblasts in placental villi, as well as the high proliferative activity that is characteristic of the early stages of gestation. Unlike erythroid progenitor cells, trophoblast infection occurs independently of erythropoietin signaling. These findings broaden the known erythroid tropism of B19V to include trophoblast cells, providing a mechanistic explanation for the heightened vulnerability of the early placenta to B19V.