scholarly journals Hepatitis E and Pregnancy: An Unholy Alliance Unmasked from Kashmir, India

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1329
Author(s):  
Mohammad Sultan Khuroo
Keyword(s):  
Viral Replication ◽  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Polymerase Activity ◽  
Severe Liver ◽  
Reading Frame ◽  
Multiple Factors ◽  
Severe Liver Disease ◽  
Development And Management

The adverse relationship between viral hepatitis and pregnancy in developing countries had been interpreted as a reflection of retrospectively biased hospital-based data collection by the West. However, the discovery of hepatitis E virus (HEV) as the etiological agent of an epidemic of non-A, non-B hepatitis in Kashmir, and the documenting of the increased incidence and severity of hepatitis E in pregnancy via a house-to-house survey, unmasked this unholy alliance. In the Hepeviridae family, HEV-genotype (gt)1 from genus Orthohepevirus A has a unique open reading frame (ORF)4-encoded protein which enhances viral polymerase activity and viral replication. The epidemics caused by HEV-gt1, but not any other Orthohepevirus A genotype, show an adverse relationship with pregnancy in humans. The pathogenesis of the association is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the pregnant women including infection and damage to the maternal-fetal interface by HEV-gt1; vertical transmission of HEV to fetus causing severe fetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the pregnant women, promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of acute liver failure. (ALF). Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

scholarly journals Hepatitis E and Pregnancy: An Unholy Alliance

2021 ◽  
Author(s):  
Mohammad Sultan Khuroo
Keyword(s):  
Viral Replication ◽  
Hepatitis E ◽  
Polymerase Activity ◽  
Maternal Outcomes ◽  
Severe Liver ◽  
The West ◽  
Multiple Factors ◽  
The Family ◽  
Severe Liver Disease ◽  
Development And Management

The adverse relationship between viral hepatitis and pregnancy in developing countries was seen as a reflection of retrospective biased hospital-based data collection by the West. However, the discovery of HEV from an epidemic of non-A, non-B hepatitis in Kashmir and documenting increased incidence and severity of hepatitis E in pregnancy from a house-to-house survey unmasked the unholy alliance. Among the family of HEV’s, genotype (gt)-1, with a unique ORF4-encoded protein enhancing viral polymerase activity and viral replication, is the sole HEV that shows this adverse relationship. The epidemics caused by HEV-gt1 and not by HEV-gt2 show adverse relationship with pregnancy. The pathogenesis of the unholy alliance is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the mother including: infection, replication and damage to the maternal-foetal interface by HEV-gt1; vertical transmission of HEV to foetus causing severe foetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the mother promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of ALF. Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

scholarly journals Ectopic Expression of Genotype 1 Hepatitis E Virus ORF4 Increases Genotype 3 HEV Viral Replication in Cell Culture

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 75
Author(s):  
Kush K. Yadav ◽  
Patricia A. Boley ◽  
Zachary Fritts ◽  
Scott P. Kenney
Keyword(s):  
Cell Culture ◽  
Viral Replication ◽  
Pregnant Women ◽  
Cell Lines ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Target Cells ◽  
Genotype 1 ◽  
Orf4 Protein

Hepatitis E virus (HEV) can account for up to a 30% mortality rate in pregnant women, with highest incidences reported for genotype 1 (gt1) HEV. Reasons contributing to adverse maternal-fetal outcome during pregnancy in HEV-infected pregnant women remain elusive in part due to the lack of a robust tissue culture model for some strains. Open reading frame (ORF4) was discovered overlapping ORF1 in gt1 HEV whose protein expression is regulated via an IRES-like RNA element. To experimentally determine whether gt3 HEV contains an ORF4-like gt1, gt1 and gt3 sequence comparisons were performed between the gt1 and the homologous gt3 sequence. To assess whether ORF4 protein could enhance gt3 replication, Huh7 cell lines constitutively expressing ORF4 were created and used to assess the replication of the Kernow-C1 gt3 and sar55 gt1 HEV. Virus stocks from transfected Huh7 cells with or without ORF4 were harvested and infectivity assessed via infection of HepG2/C3A cells. We also studied the replication of gt1 HEV in the ORF4-expressing tunicamycin-treated cell line. To directly show that HEV transcripts have productively replicated in the target cells, we assessed events at the single-cell level using indirect immunofluorescence and flow cytometry. Despite not naturally encoding ORF4, replication of gt3 HEV was enhanced by the presence of gt1 ORF4 protein. These results suggest that the function of ORF4 protein from gt1 HEV is transferrable, enhancing the replication of gt3 HEV. ORF4 may be utilized to enhance replication of difficult to propagate HEV genotypes in cell culture. IMPORTANCE: HEV is a leading cause of acute viral hepatitis (AVH) around the world. The virus is a threat to pregnant women, particularly during the second and third trimester of pregnancy. The factors enhancing virulence to pregnant populations are understudied. Additionally, field strains of HEV remain difficult to culture in vitro. ORF4 was recently discovered in gt1 HEV and is purported to play a role in pregnancy related pathology and enhanced replication. We present evidence that ORF4 protein provided in trans enhances the viral replication of gt3 HEV even though it does not encode ORF4 naturally in its genome. These data will aid in the development of cell lines capable of supporting replication of non-cell culture adapted HEV field strains, allowing viral titers sufficient for studying these strains in vitro. Furthermore, development of gt1/gt3 ORF4 chimeric virus may shed light on the role that ORF4 plays during pregnancy.

Increased oestradiol in hepatitis E virus-infected pregnant women promotes viral replication

2018 ◽  
Vol 25 (6) ◽  
pp. 742-751 ◽  
Author(s):  
C. Yang ◽  
W. Yu ◽  
Y. Bi ◽  
F. Long ◽  
Y. Li ◽  
...  
Keyword(s):  
Viral Replication ◽  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Hepatitis E

scholarly journals Advances in Hepatitis E Virus Biology and Pathogenesis

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 267
Author(s):  
Shaoli Lin ◽  
Yan-Jin Zhang
Keyword(s):  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Case Fatality ◽  
Hepatitis E ◽  
Host Cells ◽  
High Rate ◽  
Rapid Progression ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Zoonotic Infections

Hepatitis E virus (HEV) is one of the causative agents for liver inflammation across the world. HEV is a positive-sense single-stranded RNA virus. Human HEV strains mainly belong to four major genotypes in the genus Orthohepevirus A, family Hepeviridae. Among the four genotypes, genotype 1 and 2 are obligate human pathogens, and genotype 3 and 4 cause zoonotic infections. HEV infection with genotype 1 and 2 mainly presents as acute and self-limiting hepatitis in young adults. However, HEV infection of pregnant women with genotype 1 strains can be exacerbated to fulminant hepatitis, resulting in a high rate of case fatality. As pregnant women maintain the balance of maternal-fetal tolerance and effective immunity against invading pathogens, HEV infection with genotype 1 might dysregulate the balance and cause the adverse outcome. Furthermore, HEV infection with genotype 3 can be chronic in immunocompromised patients, with rapid progression, which has been a challenge since it was reported years ago. The virus has a complex interaction with the host cells in downregulating antiviral factors and recruiting elements to generate a conducive environment of replication. The virus-cell interactions at an early stage might determine the consequence of the infection. In this review, advances in HEV virology, viral life cycle, viral interference with the immune response, and the pathogenesis in pregnant women are discussed, and perspectives on these aspects are presented.

scholarly journals Antigenic Characterization of ORF2 and ORF3 Proteins of Hepatitis E Virus (HEV)

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1385
Author(s):  
Giulia Pezzoni ◽  
Lidia Stercoli ◽  
Eleonora Pegoiani ◽  
Emiliana Brocchi
Keyword(s):  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Recombinant Antigen ◽  
Open Reading Frame ◽  
Reading Frame ◽  
E Coli ◽  
Antigenic Characterization ◽  
Antigenic Properties ◽  
Open Reading Frame 2

To evaluate the antigenic properties of Hepatitis E Virus (HEV) Open Reading Frame 2 and 3 (ORF2 and ORF3) codified proteins, we expressed different portions of ORF2 and the entire ORF3 in E. coli, a truncated ORF2, was also expressed in baculovirus. A panel of 37 monoclonal antibodies (MAbs) was raised against ORF2 (1–660 amino acids) and MAbs were mapped and characterized using the ORF2 expressed portions. Selected HEV positive and negative swine sera were used to evaluate ORF2 and ORF3 antigens’ immunogenicity. The MAbs were clustered in six groups identifying six antigenic regions along the ORF2. Only MAbs binding to the sixth ORF2 antigenic region (394–608 aa) were found to compete with HEV positive sera and efficiently catch the recombinant antigen expressed in baculovirus. The ORF2 portion from 394–608 aa demonstrated to include most immunogenic epitopes with 85% of HEV positive swine sera reacting against the region from 461–544 aa. Only 5% of the selected HEV sera reacted against the ORF3 antigen.

Hepatitis E virus open reading frame 3 protein interacts with porcine liver-specific plasminogen and α2-antiplasmin

2013 ◽  
Vol 86 (3) ◽  
pp. 487-495 ◽  
Author(s):  
Yan Zhou ◽  
Yansheng Geng ◽  
Jun Yang ◽  
Chenyan Zhao ◽  
Tim J. Harrison ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Open Reading Frame ◽  
Porcine Liver ◽  
Reading Frame

scholarly journals Seroprevalence of hepatitis E virus in pregnant women in northern Lebanon

2020 ◽  
Vol 26 (5) ◽  
pp. 580-585
Author(s):  
Mohamad Bashar Ismail ◽  
Safaa Khodor ◽  
Marwan Osman ◽  
Hassan Mallat ◽  
Fouad Dabboussi ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Hepatitis E

SEROPREVALENCE OF HEPATITIS E VIRUS (HEV) INFECTION AMONG PREGNANT WOMEN IN SOUTH INDIA

2021 ◽  
pp. 28-31
Author(s):  
Nivedhitha E ◽  
Selvi R ◽  
Kayalvili KK ◽  
Arul selvan S ◽  
Duraivel M
Keyword(s):  
Drinking Water ◽  
Pregnant Women ◽  
Hepatitis E Virus ◽  
South India ◽  
Educational Status ◽  
Hepatitis E ◽  
Elisa Test ◽  
Public Health Issue ◽  
Water Type ◽  
Mortality And Morbidity

Background: Hepatitis E virus (HEV) infection poses a major public health issue in countries with poor drinking water supply, inadequate rd sanitation and improper disposal of human excretes. It causes fulminant hepatitis in pregnant women during 3 trimester with a high mortality rate of 20-30%. Aim:The aim of the study was to estimate the seroprevalence of HEVinfection among pregnant women in South India. Materials and methods: Atotal of 200 asymptomatic, pregnant women were included in the study was evaluated using a questionnaire form. 5ml of blood samples were collected from them and serum was separated to detect for the presence of HEV-antibodies and HEV-RNA by ELISA test and RT-PCR test respectively. Results: The prevalence of HEV-antibodies was found to be 11.5%. HEV-RNA was not present in any participants. A very high statistical signicance was seen associated with the risk factors such as educational status, source of drinking water, type of toilet system used, and the habit of hand washing after using toilets (P<0.01). Conclusion: Even though the prevalence of HEV among the pregnant women is low, periodic assessment and screening of the pregnant women should be done. Encouraging the public sector to strictly adhere to the personal hygienic measures will denitely have an impact in the maternal as well as perinatal mortality and morbidity

scholarly journals Hepatitis E virus infection in pregnant women, Argentina

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Gabriela Tissera ◽  
María Cecilia Lardizabal ◽  
Sofía Belén Torres ◽  
Anabella Clara Fantilli ◽  
Maribel G. Martínez Wassaf ◽  
...  
Keyword(s):  
Virus Infection ◽  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Hepatitis E
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