Evidence of extrahepatic replication of hepatitis E virus in human placenta

Abstract

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.

Experimental infection of pregnant rabbits with hepatitis E virus demonstrating high mortality and vertical transmission

“…The absence of HEV RNA in serum suggested that the detection of HEV RNA and antigen in the placental tissues was not caused by contamination of HEV RNA in circulating blood, which provided conclusive evidence for HEV replication in the placenta. These findings were consistent with the results of HEV replication in human placenta . Although the transmission of HEV through the faecal–oral route between the pregnant rabbits and their newborn rabbits could not be ignored during the breastfeeding period, it is unlikely to have happened in this study because the newborn rabbits were separated from their mothers’ cages unless it was time for suckling.…”

Hepatitis E virus replication and interferon responses in human placental cells

“…In this study, we characterized human placental‐derived cells for their permissiveness to HEV replication and analyzed antiviral mechanisms by drug treatment as well as host innate immune responses. By the detection of HEV negative‐strand RNA and antigen using immunohistochemistry in placental tissue sections of infected pregnant woman, extrahepatic replication in the placenta has been postulated 37. We report here that the placental‐derived cell line JEG‐3 supported replication of gt1 and gt3 with efficiency similar to human liver cells (Figs.…”

Prevention and Management of Viral Hepatitis in Pregnancy

“…High rates of preterm delivery and perinatal mortality have been reported. 91,92 A recent prospective study of 36 HEV-positive pregnant women in India found significantly higher rates of encephalopathy (30.5%), coagulopathy (72.2%), and intrauterine demise (55.5%) when compared with HBV-positive pregnancies. Further, all maternal deaths (n 5 5) occurred in HEV-positive women.…”

“…Women with HEV during pregnancy have higher viral loads that are Viral Hepatitis During Pregnancy proportional to disease severity. 92,94 Studies of pregnancy outcomes in industrialized, nonendemic countries are lacking. In a recent study from France, HEV seroprevalence during pregnancy was unexpectedly high (29.3%) in contrast to the lack of symptomatic disease, suggesting that most infection during pregnancy was subclinical or asymptomatic.…”