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 Hepatitis E Virus Genotype 3 in Sewage and Genotype 1 in Acute Hepatitis Cases, Israel

2016 ◽  
Vol 95 (1) ◽  
pp. 216-220 ◽  
Author(s):  
Daniela Ram ◽  
Yael Gozlan ◽  
Ella Mendelson ◽  
Orna Mor ◽  
Ziv Ben-Ari ◽  
...  
Keyword(s):  
Acute Hepatitis ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Virus Genotype

scholarly journals Detection of Hepatitis E Virus-Specific Immunoglobulin A in Patients Infected with Hepatitis E Virus Genotype 1 or 3

2007 ◽  
Vol 14 (3) ◽  
pp. 276-280 ◽  
Author(s):  
M. Herremans ◽  
E. Duizer ◽  
E. Jusic ◽  
M. P. G. Koopmans
Keyword(s):  
Acute Hepatitis ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Route Of Transmission

ABSTRACT Currently, diagnosis of acute hepatitis E virus (HEV) in patients is primarily based on anti-HEV immunoglobulin M (IgM) detection. However, several investigations suggest the use of HEV-specific IgA for diagnosing acute HEV infections. We evaluated two commercially available assays, an IgA enzyme-linked immunosorbent assay (ELISA) (Diacheck) and an adapted immunoblot protocol (Mikrogen) for IgA detection and compared the performance in genotype 1- and 3-infected patients. The specificity of the IgA assays was high, with no positive reactions in a control group of 18 acute hepatitis patients who were negative for HEV. The sensitivity calculated in nine PCR-positive type 1-infected patients was 100% in both assays but was clearly lower in genotype 3-infected patients (n = 14), with sensitivities of only 67% and 57% for the ELISA and immunoblot assay, respectively. The lower IgA responses detected in genotype 3-infected patients could be caused by the use of only the genotype 1 and 2 antigens in the serological assays. Interestingly in two patients with possible infection through blood transfusion no response or intermediate IgA responses were detected, and this might confirm the parenteral route of transmission. In both the type 1- and type 3-infected patients both the IgA and IgM responses disappeared simultaneously. We conclude that IgA detection is of limited value for the serodiagnosis of acute HEV cases, particularly with genotype 3.

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.

scholarly journals Association of poor virus specific immunoglobulin G antibody responses with higher viral load is seen in Bangladeshi pregnant women having acute Hepatitis E Genotype 1 infection

2020 ◽  
Author(s):  
Rosy Sultana ◽  
Md Tarikul Islam ◽  
Golam Sarower Bhuyan ◽  
Farjana Akther Noor ◽  
Suprovath Kumar Sarker ◽  
...  
Keyword(s):  
Viral Load ◽  
Acute Hepatitis ◽  
Pregnant Women ◽  
South Asian ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Genotype 1 ◽  
Asian Countries ◽  
Igg Antibody ◽  
Acute Hepatitis E

AbstractAlthough Hepatitis E viral illness is usually self-limiting, higher rates of morbidity and mortality are frequently observed during pregnancy in South Asian countries including Bangladesh. Of the four common variants, hepatitis E virus genotype 1 is mainly prevalent in South Asian countries. Pregnant women usually suffer from a state of immunosuppression. It is yet to be known whether virus specific immunoglobulin G (IgG) immune responses have any association with the vulnerability of pregnant women to acute hepatitis with E virus. The study aimed to compare the viral load and IgG responses of hepatitis E-infected pregnant women with that of non-pregnant women with same infection. Real Time –quantitative reverse transcription Polymerase Chain Reaction and Sanger sequencing were performed to determine the viral load and genotype, respectively, whereas Enzyme Linked Immunosorbent Assay method was used to determine hepatitis E virus specific serum IgG antibody index along with IgG avidity index. Although significant negative correlations were observed between log viral copy number and log IgG antibody index in the late acute phases of jaundice for both pregnant (r= −0.7971, p=0.0002) and non-pregnant women (r= −0.9117, p=0.0002), serum log viral copy number of pregnant women was significantly higher than that of the non-pregnant counterpart (p=0.0196) in the late acute stage of jaundice. In addition, log hepatitis E virus IgG antibody index of pregnant women was significantly lower than the non-pregnant women in the late phase of jaundice induced by hepatitis E virus (p=0.0303). Moreover, pregnant women with acute hepatitis E had higher cross-reactive IgG than in the non-pregnant women (p=0.0017). All the patients got infected with hepatitis E virus were in Genotype 1 variety. The study demonstrates that virus-specific poor IgG responses might be responsible for vulnerability of pregnant women to acute hepatitis with hepatitis E virus.Author SummaryAcute hepatitis caused by hepatitis E virus (HEV) Genotype 1 is a public health problem in Asian countries and especially it poses a potential health threat to pregnant women causing 19% to 25% mortality, particularly in South Asian countries including Bangladesh. The study aimed to explore whether HEV IgG immune responses were compromised during pregnancy, which might contribute to higher viral load and disease severity. Accordingly, pregnant and non-pregnant women with acute hepatitis (clinically presented with nausea, loss of appetite and /or jaundice) were enrolled from different tertiary care hospitals in Dhaka city. All these patients were screened and hepatitis E were differentiated from other hepatitis (caused by A, B, C) using Enzyme Linked Immunosorbent Assay (ELISA) methods. HEV IgG antibody/avidity indices and viral loads were measured using ELISA and real time quantitative polymerase chain reaction (RT-qPCR), respectively. The study showed that pregnant women with acute hepatitis E had lower IgG indices with higher viral load than their non-pregnant counterpart. Overall, the study revealed that virus-specific poor IgG responses might render pregnant women vulnerable to acute hepatitis E of varying degree of severity which might be associated with higher viral load.

scholarly journals Acute hepatitis caused by a novel strain of hepatitis E virus most closely related to United States strains

2001 ◽  
Vol 82 (7) ◽  
pp. 1687-1693 ◽  
Author(s):  
Yamina Kabrane-Lazizi ◽  
Mingdong Zhang ◽  
Robert H. Purcell ◽  
Kirk D. Miller ◽  
Richard T. Davey ◽  
...  
Keyword(s):  
United States ◽  
Phylogenetic Analysis ◽  
Acute Hepatitis ◽  
Sequence Comparison ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Aetiological Agent ◽  
Genotype 1 ◽  
Genotype 3 ◽  
The Us

A unique hepatitis E virus (HEV) strain was identified as the aetiological agent of acute hepatitis in a United States (US) patient who had recently returned from vacation in Thailand, a country in which HEV is endemic. Sequence comparison showed that this HEV strain was most similar, but not identical, to the swine and human HEV strains recovered in the US. Phylogenetic analysis revealed that this new HEV isolate was closer to genotype 3 strains than to the genotype 1 strains common in Asia. The fact that this HEV was closely related to strains recovered in countries where HEV is not endemic and was highly divergent from Asian HEV strains raises the questions of where the patient’s infection was acquired and of whether strains are geographically as localized as once thought.

Hepatitis E virus genotyping in Pakistan: a regional study to explore the implications for pregnant females

2021 ◽  
Author(s):  
Mahnoor Nadeem ◽  
Tahir Ahmad ◽  
Salik Javed Kakar ◽  
Fazal Adnan ◽  
Sadia Anjum
Keyword(s):  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Acute Infection ◽  
Hepatitis E ◽  
Immunoglobulin M ◽  
Genotype 1 ◽  
Regional Study ◽  
Third Trimester ◽  
Pregnant Females ◽  
Diagnostic Center

Aim: Hepatitis E virus (HEV) has different genotypes 1–4, which is generally associated with mild to severe complications among immunocompromised patients and pregnant women. Materials & methods: Immunoglobulin M (IgM) HEV-positive samples were collected from the diagnostic center. HEV infection was further confirmed by RT-based PCR and genotyping was done to affirm the prevailing genotype. Results: This study identified 28 patients from Islamabad who were confirmed to have immunoglobulins type M against HEV showing acute infection, of which 17 were pregnant and 11 were non-pregnant women. All pregnant women were in their third trimester of pregnancy. Conclusion: Genotype-1 is commonly associated with pregnant females presenting with HEV infections in Islamabad. There is a need to further identify both the sources & route of infections.

scholarly journals Proteomic Comparative Analysis of Pregnancy Serum Facilitating Hepatitis E Virus Replication in Hepatoma Cells

2017 ◽  
Author(s):  
Yi Li ◽  
Yanhong Bi ◽  
Wenhai Yu ◽  
Chenchen Yang ◽  
Jue Wang ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Hepatoma Cells ◽  
Host Cells ◽  
Differentially Expressed ◽  
Differentially Expressed Proteins ◽  
Absolute Quantitation

Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide, accounting for approximately 25% of deaths among pregnant women. We previously reported that pregnancy serum facilitates HEV replication in vitro. However, the differences in host cells with HEV infection induced by pregnancy serum and fetal bovine serum (FBS) are unclear. In this study, differentially expressed proteins were identified in HEV-infected hepatoma cells (HepG2) supplemented with different sera by using isobaric tags for relative and absolute quantitation. Proteomic analysis indicated that HEV infection significantly induced 1014 differentially expressed proteins in HEV-infected HepG2 cells when supplemented with FBS compared with pregnancy serum. Further validation by Western blot confirmed that filamin A, heat-shock proteins 70 and 90, Cytochrome c, and Thioredoxin were associated with HEV infection. This comparative analysis provides an important basis to further investigate HEV pathogenesis in pregnant women and HEV replication.

scholarly journals Endemic hepatitis E in two Nordic countries

2009 ◽  
Vol 14 (19) ◽  
Author(s):  
H Norder ◽  
L Sundqvist ◽  
L Magnusson ◽  
S Østergaard Breum ◽  
M Löfdahl ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Indian Subcontinent ◽  
Phylogenetic Analyses ◽  
Hepatitis E ◽  
Unknown Etiology ◽  
Genotype 1 ◽  
High Similarity ◽  
Genotype 3 ◽  
Domestic Pigs ◽  
Travel Abroad

Antibodies against hepatitis E virus (anti-HEV) were found in 248 Swedish and Danish patients between 1993 and 2007. Most patients were symptomatic and tested for anti-HEV due to travel abroad. Among patients with known country of infection, most were infected in Asia, mainly on the Indian subcontinent. However, 29 patients were infected in Europe, nine of these had HEV IgM and/or HEV RNA in serum. In sera from 65 of 141 tested patients HEV RNA could be detected, and 63 strains could be typed by limited sequencing within ORF2. HEV RNA was found in sera from 71% of the patients with HEV IgM and IgG and in 18% of the patients with only detectable HEV IgG. It was also found up to three weeks after the onset of disease in 67% of the patients with known date of onset. Patients infected in Europe were infected by genotype 3, and were older than those infected by genotype 1 (mean age 55.3 vs 30 years, p<0.001). Since it is known that genotype 3 can infect domestic pigs, HEV strains from 18 piglets in 17 herds in Sweden and Denmark were sequenced. Phylogenetic analyses of the genotype 3 strains showed geographical clades and high similarity between strains from patients and pigs from the same area. There are thus autochthonous hepatitis E cases in Scandinavia, and there are probably many undiagnosed ones. Patients with hepatitis of unknown etiology should therefore be investigated for anti-HEV even if they have not been outside Europe, since infections acquired from pigs or other animals should be taken into consideration.

scholarly journals Quadruple Recombination Events Discovered in Hepatitis E Virus

2021 ◽  
Author(s):  
Hao Shen ◽  
Shuning Liu ◽  
Min Ding ◽  
Haixia Gu ◽  
Ming Chang ◽  
...  
Keyword(s):  
Recombination Event ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Progeny Virus ◽  
Future Research ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Minor Parent ◽  
Detection Analysis ◽  
Orf2 Region

Abstract Hepatitis E virus (HEV) can infect humans, pigs, and many other animals, but the recombination of HEV has rarely been reported. In the present study, phylogenetic and recombination analyses were performed on 557 complete HEV genomes in GenBank. A potentially significant quadruple recombination event was identified by recombination detection analysis. The recombinant progeny virus HEV_32_Manchester_301214 was produced by recombination between the major parent HEPAC-44 and the minor parent HE-JA15-1335, thereby reflecting inter-genotype recombination. HEV_32_Manchester_301214 and HEPAC-44 belong to genotype 3, while HE-JA15-1335 belongs to genotype 1, and these three strains have all been separated from humans. Three breakpoints of the four recombination events occurred in the ORF2 region, while another occurred in the ORF1 region. This quadruple recombination event was confirmed by phylogenetic analysis. The genotype, host and the recombination regions of the three strains were analyzed. These results of the analyses provide valuable suggestions for future research on HEV diversity.

scholarly journals Use of Serological Assays for Diagnosis of Hepatitis E Virus Genotype 1 and 3 Infections in a Setting of Low Endemicity

2007 ◽  
Vol 14 (5) ◽  
pp. 562-568 ◽  
Author(s):  
M. Herremans ◽  
J. Bakker ◽  
E. Duizer ◽  
H. Vennema ◽  
M. P. G. Koopmans
Keyword(s):  
Hepatitis E Virus ◽  
Specific Antigen ◽  
Hepatitis E ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Virus Genotype ◽  
Immunoblot Assay ◽  
Specificity And Sensitivity

ABSTRACT Because of the occurrence of genotype 3 hepatitis E virus (HEV) in regions of low endemicity, it is important to validate the currently used serological assays for diagnosing infections with viruses belonging to this lineage, since these assays only use antigens derived from genotype 1 and 2 viruses. We evaluated the Genelabs enzyme-linked immunosorbent assay (ELISA) and the RecomBlot from Mikrogen for the detection of HEV-specific immunoglobulin M (IgM) and IgG under conditions of low endemicity. We compared test results of 16 patients with locally acquired genotype 3 HEV, 8 genotype 1 patients, 167 healthy controls from the general population, and 101 cases with hepatitis due to other viral causes. The measured specificities of the ELISA (98%) and the RecomBlot (97%) were comparable to those given by the manufacturer for IgM but were significantly lower for IgG (93% by ELISA and 66% by immunoblotting, versus reported values of 98% for ELISA and 95% for blotting). Antibody levels detected following infections with genotype 3 were lower than those following genotype 1 infections except for those measured in the IgM ELISA. Reactivity to the four antigens used in the immunoblot assay were analyzed and showed differences in the IgM immunoblot reactions between genotype 1 patients and genotype 3 patients. The ORF3 antigen was the most specific antigen. The specificity could be improved by a combined testing regimen with confirmation by immunoblotting of all positive ELISA results and by raising the cutoff of the IgG immunoblot assay without loss of sensitivity. We conclude that a combination of ELISA and immunoblotting is needed for acceptable specificity and sensitivity of HEV assays under conditions of low endemicity.

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