Jordi Gouilly, Qian Chen, Johan Siewiera, Géraldine Cartron, Claude Levy, Martine Dubois, Reem Al-Daccak, Jacques Izopet, Nabila Jabrane-Ferrat*, and Hicham El Costa*
Centre of Pathophysiology Toulouse Purpan, INSERM U1043, CNRS UMR5282, Toulouse III University, 31024 Toulouse, France.
Correspondence: firstname.lastname@example.org & email@example.com
In emerging countries with poor sanitation, Hepatitis E virus (HEV) infection during pregnancy often results in fulminant hepatic failure, severe placental diseases and morbidity. To provide insights into the HEV pathogenicity during pregnancy, we developed a new ex vivo model of HEV infection at the maternal-fetal interface using organ cultures from the first-trimester maternal decidua and fetal placenta and two HEV genotypes. We discovered that the pathogenic HEV-1 replicates more efficiently than less pathogenic HEV-3 in decidua and placenta explants and produces higher amounts of infectious progeny virions in a type III interferon dependent manner causing severe morphological alterations.
Our findings advocate that HEV-1 tropism and efficient replication combined with abnormal pro-inflammatory microenvironment dictate the extent of tissue damage at the maternal-fetal interface. Furthermore, we provide an innovative model with significant clinical implications for understanding congenital pathology and for developing strategies to mitigate viral trafficking through the placental barrier.