Abstract
Hepatitis E virus (HEV) infection, particularly HEV genotype 1 (HEV-1), can result in fulminant hepatic failure and severe placental diseases, but mechanisms underlying genotype-specific pathogenicity are unclear and appropriate models are lacking. Here, we model HEV-1 infection ex vivo at the maternal-fetal interface using the decidua basalis and fetal placenta, and compare its effects to the less-pathogenic genotype 3 (HEV-3). We demonstrate that HEV-1 replicates more efficiently than HEV-3 both in tissue explants and stromal cells, produces more infectious progeny virions and causes severe tissue alterations. HEV-1 infection dysregulates the secretion of several soluble factors. These alterations to the cytokine microenvironment correlate with viral load and contribute to the tissue damage. Collectively, this study characterizes an ex vivo model for HEV infection and provides insights into HEV-1 pathogenesis during pregnancy that are linked to high viral replication, alteration of the local secretome and induction of tissue injuries.
Highlights
Hepatitis E virus (HEV) infection, HEV genotype 1 (HEV-1), can result in fulminant hepatic failure and severe placental diseases, but mechanisms underlying genotype-specific pathogenicity are unclear and appropriate models are lacking
We ex vivo modeled HEV infections at the maternal-fetal interface using organ cultures of the maternal decidua and fetal placenta from elective pregnancy terminations and examined their susceptibility to clinical strains of HEV-1 and HEV-3 isolated at the acute phase of infection from the feces of a traveler returning from India and an autochthone infected patient, respectively
Using an ex vivo model of first trimester maternal-fetal interface, we provide here the first evidence that the decidua and the placenta are prone to HEV-1 infection rather than HEV-3, resulting in the generation of infectious progeny virions
Summary
Hepatitis E virus (HEV) infection, HEV genotype 1 (HEV-1), can result in fulminant hepatic failure and severe placental diseases, but mechanisms underlying genotype-specific pathogenicity are unclear and appropriate models are lacking. These authors contributed : Nabila Jabrane-Ferrat, Hicham El Costa. In countries with poor sanitation, HEV-1 infection during pregnancy often results in fulminant hepatic failure (FHF, in 15–30% of cases) associated with severe placental diseases, including eclampsia, hemorrhage, membrane rupture, spontaneous abortion, and stillbirths[2,4]. These fatal outcomes resemble those reported for other harmful pathogens during pregnancy and can be attributed to dysfunctions at the maternalfetal interface composed of the pregnant endometrium lining or decidua basalis (decidua), and fetal placenta[5,6,7]. Only a single study identified viral components in placental tissue from HEV-1-infected women, suggesting the placenta as an extra-hepatic site for viral replication[13]
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