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Open AccessArticle

Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells

1
Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt
2
Reproductive Science Research Center, Assiut University, 71515 Assiut, Egypt
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Department of Obstetrics and Gynecology, Assiut University, 71515 Assiut, Egypt
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Department of Reproductive Medicine, Academic Endometriosis Center, Amsterdam University Medical Center, Postbus 22660, 1100 DD Amsterdam, The Netherlands
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Department of Internal Medicine, Faculty of Medicine, Zagazig University, 44519 Zagazig, Egypt
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Department of Tropical Medicine and Gastroenterology Department, Assiut University, 71515 Assiut, Egypt
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Department of Clinical Pathology, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt
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Department of Pathology, School of Medicine, University of California, San Diego, CA 92093, USA
*
Author to whom correspondence should be addressed.
Pathogens 2020, 9(4), 295; https://doi.org/10.3390/pathogens9040295
Received: 23 March 2020 / Revised: 10 April 2020 / Accepted: 14 April 2020 / Published: 17 April 2020
(This article belongs to the Special Issue Global Elimination of Viral Hepatitis)
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. The tropism of HEV is not restricted to the liver, and the virus replicates in other organs. Not all the extrahepatic targets for HEV are identified. Herein, we found that non-decidualized primary human endometrial stromal cells (PHESCs), which are precursors for the decidua and placenta, are susceptible to HEV infection. PHESCs, isolated from healthy non-pregnant women (n = 5), were challenged with stool-derived HEV-1 and HEV-3. HEV RNA was measured by qPCR, and HEV capsid protein was assessed by flow cytometry, immunofluorescence (IF), and ELISA. HEV infection was successfully established in PHESCs. Intracellular and extracellular HEV RNA loads were increased over time, indicating efficient replication in vitro. In addition, HEV capsid protein was detected intracellularly in the HEV-infected PHESCs and accumulated extracellularly over time, confirming the viral assembly and release from the infected cells. HEV-1 replicated more efficiently in PHESCs than HEV-3 and induced more inflammatory responses. Ribavirin (RBV) treatment abolished the replication of HEV in PHESCs. In conclusion, PHESCs are permissive to HEV infection and these cells could be an endogenous source of HEV infection during pregnancy and mediate HEV vertical transmission. View Full-Text
Keywords: HEV; endometrial stromal cells; pathogenesis; extrahepatic replication; female genital system; pregnancy; ribavirin HEV; endometrial stromal cells; pathogenesis; extrahepatic replication; female genital system; pregnancy; ribavirin
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MDPI and ACS Style

El-Mokhtar, M.A.; Othman, E.R.; Khashbah, M.Y.; Ismael, A.; Ghaliony, M.A.; Seddik, M.I.; Sayed, I.M. Evidence of the Extrahepatic Replication of Hepatitis E Virus in Human Endometrial Stromal Cells. Pathogens 2020, 9, 295.

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