Genotype 4 Hepatitis E virus replicates in the placenta, causes severe histopathological damage, and vertically transmits to fetuses

Background Hepatitis E virus (HEV) infection in pregnant women causes adverse pregnancy outcomes, including maternal death, premature delivery, stillbirth, and fetal infection. However, the pathogenesis of maternal and fetal HEV infection is unclear. Methods Placenta and placental appendixes were collected from HEV-4 infected pregnant women to explore the vertical transmission of HEV from mothers to fetuses. Results HEV-4 replicated in the placenta, placental membrane, and umbilical cord and was vertically transmitted from mothers to fetuses. HEV-4 placental infection resulted in serious histopathological damage, such as fibrosis and calcification, and severe inflammatory responses. Adverse maternal outcomes were observed in 38.5% of HEV-4 infected pregnant women. The distinct cytokine/chemokine expression patterns of HEV-infected pregnant women and nonpregnant women may contribute to the adverse pregnancy outcomes. Furthermore, the impaired maternal and fetal innate immune responses against HEV-4 facilitated viral replication during pregnancy. Conclusion HEV-4 replicates in the placenta and is vertically transmitted from mothers to fetuses, causing severe histopathological damage.