Hepatitis E Virus Infection: Neurological Manifestations and Pathophysiology

Lhomme, Sébastien; Abravanel, Florence; Cintas, Pascal; Izopet, Jacques

doi:10.3390/pathogens10121582

Cited by 17 publications

(11 citation statements)

References 96 publications

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“…Ribavirin (RBV) is commonly administrated as an off-label treatment for chronic hepatitis E (CHE), but significant side effects often limit its use ( 5 , 6 ). In addition to FHF and CHE, HEV is also associated with a wide range of extrahepatic manifestations ( 7 ). HEV-associated FHF, CHE, and neurological sequelae all require effective antiviral therapy, but unfortunately, an HEV-specific direct-acting antiviral is still lacking.…”

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confidence: 99%

Two mutations in the ORF1 of genotype 1 hepatitis E virus enhance virus replication and may associate with fulminant hepatic failure

Wang

Tian

Sooryanarain

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Hepatitis E virus (HEV) infection in pregnant women has a high incidence of developing fulminant hepatic failure (FHF) with significant mortality. Multiple amino acid changes in genotype 1 HEV (HEV-1) are reportedly linked to FHF clinical cases, but experimental confirmation of the roles of these changes in FHF is lacking. By utilizing the HEV-1 indicator replicon and infectious clone, we generated 11 HEV-1 single mutants, each with an individual mutation, and investigated the effect of these mutations on HEV replication and infection in human liver cells. We demonstrated that most of the mutations actually impaired HEV-1 replication efficiency compared with the wild type (WT), likely due to altered physicochemical properties and structural conformations. However, two mutations, A317T and V1120I, significantly increased HEV-1 replication. Notably, these two mutations simultaneously occurred in 100% of 21 HEV-1 variants from patients with FHF in Bangladesh. We further created an HEV-1 A317T/V1120I double mutant and found that it greatly enhanced HEV replication, which may explain the rapid viral replication and severe disease. Furthermore, we tested the effect of these FHF-associated mutations on genotype 3 HEV (HEV-3) replication and found that all the mutants had a reduced level of replication ability and infectivity, which is not unexpected due to distinct infection patterns between HEV-1 and HEV-3. Additionally, we demonstrated that these FHF-associated mutations do not appear to alter their sensitivity to ribavirin (RBV), suggesting that ribavirin remains a viable option for antiviral therapy for patients with FHF. The results have important implications for understanding the mechanism of HEV-1–associated FHF.

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confidence: 99%

Two mutations in the ORF1 of genotype 1 hepatitis E virus enhance virus replication and may associate with fulminant hepatic failure

Wang

Tian

Sooryanarain

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…HEV is an enteric virus responsible for both acute and chronic disorders mainly in the liver (Pischke et al, 2017). It can also cause neurological manifestations in both acutely and chronically HEVinfected patients (Cheung et al, 2012;Lhomme et al, 2021), kidneys (Kamar et al, 2012), pancreas, and thrombocytes (Aggarwal, 2011). The WHO (2021) noted about 20 million new cases of HEV infections each year, with over 3 million symptomatic cases.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis E Virus in Water Environments: A Systematic Review and Meta-analysis

et al. 2022

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Hepatitis E virus (HEV) is responsible for acute hepatitis in humans, through foodborne, zoonotic, and waterborne transmission routes. This study aimed to assess the prevalence of HEV in water matrices. Six categories were defined: untreated and treated wastewater, surface water (river, lake, and seawater), drinking water, groundwater, and other water environments (irrigation water, grey water, reservoir water, flood water, and effluent of pig slaughterhouse). We searched PubMed, Web of Science, Global Index Medicus, and Excerpta Medica Database. Study selection and data extraction were performed by at least two independent investigators. Heterogeneity (I2) was assessed using the χ2 test on the Cochran Q statistic and H parameter. Sources of heterogeneity were explored by subgroup analysis. This study is registered with PROSPERO, number CRD42021289116. We included 87 prevalence studies from 58 papers, 66.4% of which performed in Europe. The overall prevalence of HEV in water was 9.8% (95% CI 6.4–13.7). The prevalence was higher in untreated wastewater (15.1%) and lower in treated wastewater (3.8%) and in drinking water (4.7%). In surface water, prevalence was 7.4%, and in groundwater, the percentage of positive samples, from only one study available, was 8.3%. Overall, only 36.8% of the studies reported the genotype of HEV, with genotype 3 (HEV-3) prevalent (168 samples), followed by HEV-1 (148 sample), and HEV-4 (2 samples). High-income countries were the most represented with 59/87 studies (67.8%), while only 3/87 (3.5%) of the studies were performed in low-income countries. The overall prevalence obtained of this study was generally higher in industrialized countries. Risk of bias was low in 14.9% of the studies and moderate in 85.1%. The results of this review showed the occurrence of HEV in different waters environments also in industrialized countries with sanitation and safe water supplies. While HEV transmission to humans through water has been widely demonstrated in developing countries, it is an issue still pending in industrialized countries. Better knowledge on the source of pollution, occurrence, survival in water, and removal by water treatment is needed to unravel this transmission path. Graphical Abstract

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“…Generally, HEV viremia persisting longer than three months can be regarded as a chronic infection and considered for treatment, but treatment options for chronic hepatitis E are very limited since an HEV-specific antiviral is still lacking [ 7 , 8 ]. In addition to fulminant hepatic failure and chronic infection, HEV is also associated with a wide range of extrahepatic manifestations such as neurological and renal injuries [ 9 , 10 ]; however, the underlying molecular mechanisms contributing to the HEV-associated diseases process are poorly understood, and the decisive viral- and host-related factors responsible for relevant clinical disorders remain to be determined.…”

Section: Introductionmentioning

confidence: 99%

Chirohepevirus from Bats: Insights into Hepatitis E Virus Diversity and Evolution

Wang

Yang

2022

Viruses

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Homologs of the human hepatitis E virus (HEV) have been identified in more than a dozen animal species. Some of them have been evidenced to cross species barriers and infect humans. Zoonotic HEV infections cause chronic liver diseases as well as a broad range of extrahepatic manifestations, which increasingly become significant clinical problems. Bats comprise approximately one-fifth of all named mammal species and are unique in their distinct immune response to viral infection. Most importantly, they are natural reservoirs of several highly pathogenic viruses, which have induced severe human diseases. Since the first discovery of HEV-related viruses in bats in 2012, multiple genetically divergent HEV variants have been reported in a total of 12 bat species over the last decade, which markedly expanded the host range of the HEV family and shed light on the evolutionary origin of human HEV. Meanwhile, bat-borne HEV also raised critical public health concerns about its zoonotic potential. Bat HEV strains resemble genomic features but exhibit considerable heterogeneity. Due to the close evolutionary relationships, bat HEV altogether has been recently assigned to an independent genus, Chirohepevirus. This review focuses on the current state of bat HEV and provides novel insights into HEV genetic diversity and molecular evolution.

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Hepatitis E Virus Infection: Neurological Manifestations and Pathophysiology

Cited by 17 publications

References 96 publications

Two mutations in the ORF1 of genotype 1 hepatitis E virus enhance virus replication and may associate with fulminant hepatic failure

Two mutations in the ORF1 of genotype 1 hepatitis E virus enhance virus replication and may associate with fulminant hepatic failure

Hepatitis E Virus in Water Environments: A Systematic Review and Meta-analysis

Chirohepevirus from Bats: Insights into Hepatitis E Virus Diversity and Evolution

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