Evidence of extrahepatic replication of hepatitis E virus in human placenta

The incidence and severity of hepatitis E virus (HEV) infection in pregnant women is high in developing countries. Transplacental transmission of HEV in the third trimester of pregnancy has been found to be associated with high fetal mortality. Based on this evidence and in the absence of reports on HEV replication in extrahepatic sites, this study was carried out to investigate if HEV replication occurs in the placenta of infected mothers. The study included 68 acute viral hepatitis (AVH) and 22 acute liver failure (ALF) pregnant patients. Viral RNA was extracted from blood and placenta. HEV replication in placenta was confirmed by a replicative negative-strand-specific reverse transcriptase PCR. Viral load was estimated by real-time PCR. Immunohistochemical studies were also carried out for in situ detection of HEV in placental tissue sections. Replicative HEV RNA was detectable only in the placenta in ALF and AVH cases and not in blood samples. Positive staining of placental tissue sections with HEV antibody against the viral structural protein ORF3 was observed. HEV replication in placenta also correlated with fetal and maternal mortality in ALF patients. It is demonstrated for the first time that HEV replication occurs in human placenta and that placenta may be a site of extrahepatic replication of HEV in humans.

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P686 EXTRAHEPATIC REPLICATION OF HEPATITIS E VIRUS IN HUMAN PLACENTA: ITS CLINICAL IMPLICATIONS

Journal of Hepatology ◽

10.1016/s0168-8278(14)60848-5 ◽

2014 ◽

Vol 60 (1) ◽

pp. S297-S298

Author(s):

P. Deka ◽

B.C. Das ◽

R.K. Hazam ◽

A. Kumar ◽

P. Kar

Keyword(s):

Human Placenta ◽

Hepatitis E Virus ◽

Hepatitis E ◽

Clinical Implications ◽

Extrahepatic Replication

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P200: Extrahepatic replication of hepatitis E virus in neuronal and placental cell lines

Journal of Viral Hepatitis ◽

10.1111/jvh.183_12425 ◽

2015 ◽

Vol 22 ◽

pp. 120-121

Keyword(s):

Cell Lines ◽

Hepatitis E Virus ◽

Hepatitis E ◽

Placental Cell ◽

Extrahepatic Replication

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

Pathogens ◽

10.3390/pathogens9040295 ◽

2020 ◽

Vol 9 (4) ◽

pp. 295 ◽

Cited By ~ 5

Author(s):

Mohamed A. El-Mokhtar ◽

Essam R. Othman ◽

Maha Y. Khashbah ◽

Ali Ismael ◽

Mohamed AA Ghaliony ◽

...

Keyword(s):

Capsid Protein ◽

Stromal Cells ◽

Hepatitis E Virus ◽

Inflammatory Responses ◽

Hepatitis E ◽

Endometrial Stromal Cells ◽

Extrahepatic Replication ◽

Efficient Replication ◽

Over Time

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.

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A naturally occurring human/hepatitis E recombinant virus predominates in serum but not in faeces of a chronic hepatitis E patient and has a growth advantage in cell culture

Journal of General Virology ◽

10.1099/vir.0.037259-0 ◽

2012 ◽

Vol 93 (3) ◽

pp. 526-530 ◽

Cited By ~ 56

Author(s):

H. T. Nguyen ◽

U. Torian ◽

K. Faulk ◽

K. Mather ◽

R. E. Engle ◽

...

Keyword(s):

Hepatitis E Virus ◽

Cultured Cells ◽

Hypervariable Region ◽

Hepatitis E ◽

Structural Protein ◽

Chronic Infections ◽

Virus Growth ◽

Acute Hepatitis E ◽

A Minor ◽

Virus Genomes

Hepatitis E virus is the aetiological agent of acute hepatitis E, a self-limiting disease prevalent in developing countries. Molecular analysis of viral genomic RNA from a chronically infected patient confirmed the recent discovery that chronic infection correlated with extensive diversification of the virus quasispecies: the hypervariable region of some virus genomes in this USA patient contained large continuous deletions and a minor proportion of genomes in faeces and serum had acquired a mammalian sequence that encoded 39 aa of S19 ribosomal protein fused to the virus non-structural protein. Genomes with this insert were selected during virus passage in cultured cells to become the predominant species, suggesting that the inserted sequence promoted virus growth. The results demonstrated that hepatitis E virus can mutate dramatically during a prolonged infection and suggests it may be important to prevent or cure chronic infections before new variants with unpredictable properties arise.

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Hepatitis E virus (HEV)-1 harbouring HEV-4 non-structural protein (ORF1) replicates in transfected porcine kidney cells

Journal of General Virology ◽

10.1099/jgv.0.000478 ◽

2016 ◽

Vol 97 (8) ◽

pp. 1829-1840 ◽

Cited By ~ 12

Author(s):

Subhashis N. Chatterjee ◽

Pradip B. Devhare ◽

Shweta Y. Pingle ◽

Mandar S. Paingankar ◽

Vidya A. Arankalle ◽

...

Keyword(s):

Hepatitis E Virus ◽

Hepatitis E ◽

Kidney Cells ◽

Porcine Kidney ◽

Structural Protein

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Hepatitis E Virus Infection During Pregnancy: The Overlooked Cause of Maternal and Fetal Mortality

Infectious Disorders - Drug Targets ◽

10.2174/1871526518666180530075523 ◽

2019 ◽

Vol 19 (3) ◽

pp. 334-336 ◽

Cited By ~ 2

Author(s):

Fatemeh Farshadpour ◽

Sakineh Taherkhani ◽

Reza Taherkhani

Keyword(s):

Pregnant Women ◽

High Frequency ◽

Hepatitis E Virus ◽

Preventive Measures ◽

Training Programs ◽

Hepatitis E ◽

Fetal Mortality ◽

Prophylactic Vaccine ◽

Proper Treatment ◽

Geographical Locations

Background: Hepatitis E virus (HEV) is one the leading causes of maternal and fetal mortality. Nevertheless, in some geographical locations, especially Egypt, despite having high frequency of HEV seropositivity, HEV infection follows an asymptomatic or mild course during pregnancy. These anomalous observations have distracted attention from the importance of HEV infection in pregnant women. Methods: While tragic cases of HEV-infected pregnant women cannot be neglected any longer. Conclusion: These circumstances create a strong demand for the increasing awareness of HEV infection through training programs, appropriate management of HEV infection among pregnant women, routine screening of pregnant women for timely diagnosis of HEV infection, proper treatment of HEVinfected patients, optimal preventive measures, and development of a prophylactic vaccine against HEV infection.

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