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Nat Commun. 2018 Nov 12;9(1):4748. doi: 10.1038/s41467-018-07200-2.

Genotype specific pathogenicity of hepatitis E virus at the human maternal-fetal interface.

Author information

1
Centre of Pathophysiology Toulouse Purpan, INSERM U1043, CNRS UMR5282, Toulouse III University, 31024, Toulouse, France.
2
University of California San Francisco, School of Medicine, Laboratory of Medicine, San Francisco, CA, USA.
3
Service de Gynécologie-Obstétrique, Hôpital Paule de Viguier, Centre Hospitalier Universitaire, 31059, Toulouse, France.
4
Service de Gynécologie-Obstétrique, Clinique Sarrus-Teinturiers, 31300, Toulouse, France.
5
Laboratoire de Virologie, Institute of Federative Biology, Centre Hospitalier Universitaire, 31059, Toulouse, France.
6
INSERM UMRS976, Université Paris Diderot, Hôpital Saint-Louis, 75010, Paris, France.
7
Centre of Pathophysiology Toulouse Purpan, INSERM U1043, CNRS UMR5282, Toulouse III University, 31024, Toulouse, France. nabila.jabrane-ferrat@inserm.fr.
8
Centre of Pathophysiology Toulouse Purpan, INSERM U1043, CNRS UMR5282, Toulouse III University, 31024, Toulouse, France. hicham.el-costa@inserm.fr.
9
Laboratoire de Virologie, Institute of Federative Biology, Centre Hospitalier Universitaire, 31059, Toulouse, France. hicham.el-costa@inserm.fr.

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.

PMID:
30420629
PMCID:
PMC6232144
DOI:
10.1038/s41467-018-07200-2
[Indexed for MEDLINE]
Free PMC Article

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