{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:29:24Z","timestamp":1790022564964,"version":"4.0.1"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,3,24]],"date-time":"2022-03-24T00:00:00Z","timestamp":1648080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Viral hepatitis E is an under\u2010estimated clinical entity with high mortality (20%\u201330%), especially in the third trimester of pregnancy. As complications due to hepatitis E virus (HEV) in pregnancy is much greater, it is hypothesized that HEV may cross the placenta and replicate in placental tissues even weeks after clearance from the blood, and cytokines may play a role in the immunopathogenesis of HEV in pregnancy. A total of 12 pregnant women with features of acute viral hepatitis\/acute liver failure and positive for either HEV\u2010immunoglobulin M (IgM)\/HEV\u2010RNA and 30 pregnant women negative for HEV RNA\/IgM\/immunoglobulin G were enrolled as study subjects and healthy controls, respectively. Following delivery, 5\u2009ml blood was collected from the mother for HEV\u2010RNA. Replicative RNA and viral load in placental tissue were detected through Real\u2010Time PCR. Placental tissues from the maternal\/fetal sides were stained for HEV antigen using HEV\u2010open reading frame\u20102 antibody by immunohistochemistry (IHC) and for histopathological changes by haematoxylin and eosin. Plasma samples were tested for interleukin (IL)\u20101\u03b2 and IL\u201018 cytokine levels using Duo\u2010R&amp;D ELISA kit, whereas peripheral blood mononuclear cells were used to study the inflammasomes and IL\u20101\u03b2 and IL\u201018 cytokine genes expression.Of the 10 HEV RNA\u2010positive sera, 9 had HEV RNA either in the maternal\/fetal side of the placenta with the mean viral load of 137.4\u2009IU\/ml. Of the 10 HEV RNA\u2010positive pregnant women, stillbirth in two and fetal and maternal death in one case was reported. IHC revealed strong brownish cytoplasmic staining (HEV antigen) in cytotrophoblasts and syncytiotrophoblast cells in positive samples. The maternal\/fetal side of the infected placenta showed irregular intervillous fibrin deposition as well as tissue necrosis. The mean levels of IL\u20101\u03b2 and IL\u201018 cytokines in serum of infected subjects were significantly higher than the healthy controls (17.31\u2009\u00b1\u20094.462 vs. 8.85\u2009\u00b1\u20094.36\u2009pg\/ml; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001*** and 2275\u2009\u00b1\u2009536.9 vs. 1085\u2009\u00b1\u2009531.7\u2009pg\/ml; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001***), respectively. Detecting replicative HEV RNA and HEV antigen in placental tissues indicated the extra\u2010hepatic replication of HEV. Furthermore, placental tissue necrosis and significant rise of cytokine levels in HEV\u2010infected pregnant women might be contributing to the HEV pathogenesis in pregnancy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.27699","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T23:00:13Z","timestamp":1646694013000},"page":"3457-3463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Placenta as a site of HEV replication and inflammatory cytokines modulating the immunopathogenesis of HEV in pregnant women"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7205-9325","authenticated-orcid":false,"given":"Radha Kanta","family":"Ratho","sequence":"first","affiliation":[{"name":"Department of Virology Postgraduate Institute of Medical Education and Research, PGIMER  Chandigarh 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