4.3 Review

Animal models of hepatitis E infection: Advances and challenges

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Article Virology

Serum extracellular vesicle-derived ASS1 is a promising predictor for the occurrence of HEV-ALF

Ze Xiang et al.

Summary: Development of biomarkers for predicting the occurrence of hepatitis E virus related-acute liver failure (HEV-ALF) is important for prevention and early intervention. EV-derived ASS1 levels show high predictive capability and are an independent risk factor for HEV-ALF. The AUC of EV-derived ASS1 level to predict HEV-ALF occurrence is 0.728 with high decision-making ability.

JOURNAL OF MEDICAL VIROLOGY (2023)

Article Virology

Efficacy of an accelerated vaccination schedule against hepatitis E virus infection in pregnant rabbits

Fan Zhang et al.

Summary: This study demonstrated that the HEV vaccine could induce high titers of protective antibodies against HEV in pregnant rabbits within a short period of time, and these antibodies could be transferred to neonates through the placenta and breast milk, providing protection against HEV infection. This suggests that HEV 239 vaccine could be considered for maternal vaccination.

JOURNAL OF MEDICAL VIROLOGY (2023)

Article Virology

Experimental Cross-Species Transmission of Rat Hepatitis E Virus to Rhesus and Cynomolgus Monkeys

Fengmei Yang et al.

Summary: Through experimental studies, it was found that cynomolgus and rhesus monkeys are susceptible to rat hepatitis E virus (rat HEV) and may cause zoonotic infections. These findings provide an animal model for the development of vaccines.

VIRUSES-BASEL (2022)

Article Veterinary Sciences

Research on a rat model of genotype IV swine hepatitis E virus

Zhijie Jian et al.

Summary: The study successfully established a rat infection model, demonstrating that porcine hepatitis E virus can infect rats across species and viral RNA can be detected in multiple tissues and organs. This provides new insights and scientific basis for studying the mechanism of HEV infection and preventing HEV infection.

VETERINARY MEDICINE AND SCIENCE (2022)

Article Pharmacology & Pharmacy

High dose sofosbuvir and sofosbuvir-plus-ribavirin therapy inhibit Hepatitis E Virus (HEV) replication in a rabbit model for acute HEV infection

Zhaochao Liang et al.

Summary: This study found that high doses of SOF have an inhibitory effect on HEV genotype 3 and 4 in a rabbit model, and SOF plus RBV therapy showed stronger anti-HEV effects compared to RBV monotherapy.

ANTIVIRAL RESEARCH (2022)

Article Gastroenterology & Hepatology

Immunocompromised rabbit model of chronic HEV reveals liver fibrosis and distinct efficacy of different vaccination strategies

Qiyu He et al.

Summary: By using an immunocompromised rabbit model, chronic HEV3 and HEV4 infections were successfully established, capturing the key features of chronic infection and revealing different effects of vaccination before and during immunosuppression.

HEPATOLOGY (2022)

Article Virology

Mongolia Gerbils Are Broadly Susceptible to Hepatitis E Virus

Wenjing Zhang et al.

Summary: Mongolia gerbils are broadly susceptible to different genotypes of HEV, making them a useful animal model for studying HEV infection and evaluating vaccine effectiveness.

VIRUSES-BASEL (2022)

Article Virology

The diagnostic and prognostic value of serum exosome-derived carbamoyl phosphate synthase 1 in HEV-related acute liver failure patients

Ze Xiang et al.

Summary: This study found that serum exosome-derived CPS1 levels were significantly elevated in HEV-ALF patients and were closely associated with organ failure and prognosis. Serum exosome-derived CPS1 levels may serve as a promising diagnostic and prognostic biomarker for HEV-ALF patients.

JOURNAL OF MEDICAL VIROLOGY (2022)

Article Virology

Characterization of Chronic Hepatitis E Virus Infection in Immunocompetent Rabbits

Chunnan Liang et al.

Summary: We characterized the course of chronic HEV infection in immunocompetent rabbits and found that 47.5% of the rabbits developed chronic infection with persistent viral shedding for more than 6 months.

VIRUSES-BASEL (2022)

Article Microbiology

Hepatitis E Virus (HEV): Identification of Subtypes 3b and 3m in Wild Boar Population in Liguria Region, Italy

Roberta Battistini et al.

Summary: Wild boars are important natural reservoirs for the zoonotic transmission of hepatitis E virus (HEV) worldwide. This study investigated the prevalence and geographic circulation of HEV among wild boar populations in the Ligurian region of Italy. The results showed an increase in the percentage of HEV-positive wild boars in the last two years, as well as different circulations of identified subtypes across the territory.

PATHOGENS (2022)

Article Multidisciplinary Sciences

Hepatitis E virus infects brain microvascular endothelial cells, crosses the blood-brain barrier, and invades the central nervous system

Debin Tian et al.

Summary: This study demonstrates that the hepatitis E virus (HEV) can cross the blood-brain barrier and both quasi-enveloped and nonenveloped HEVs have similar abilities in this process. Additionally, human brain microvascular endothelial cells are susceptible to HEV infection, and similar results were observed in pigs.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

Article Gastroenterology & Hepatology

Transmission of Rat Hepatitis E Virus Infection to Humans in Hong Kong: A Clinical and Epidemiological Analysis

Siddharth Sridhar et al.

Summary: HEV-C1 virus is a cause of hepatitis E in humans in Hong Kong, immunosuppressed individuals are susceptible to persistent infection and extrahepatic manifestations, subclinical infection also threatens blood safety.

HEPATOLOGY (2021)

Article Hematology

Hepatitis E virus: Efficacy of pasteurization of plasma-derived VWF/FVIII concentrate determined by pig bioassay

Lisa Daehnert et al.

Summary: The study demonstrated that pasteurization at 60 degrees C for 10 hours of an HEV-positive plasma derivative effectively reduces infectivity, resulting in a VWF/FVIII product with an appropriate margin of safety for HEV.

TRANSFUSION (2021)

Article Virology

Uterine Injury Caused by Genotype 4 Hepatitis E Virus Infection Based on a BALB/c Mice Model

Weimin Yang et al.

Summary: Uterine injury caused by HEV infection leads to severe inflammatory responses and apoptosis, which may result in miscarriage and infertility. Thinning of endometrial thickness and altered expression levels of certain proteins may also contribute to adverse pregnancy outcomes.

VIRUSES-BASEL (2021)

Article Gastroenterology & Hepatology

Resolution of hepatitis E virus infection in CD8+T cell-depleted rhesus macaques

William Bremer et al.

Summary: The study found that CD8+ T cells can assist in controlling HEV infection in untreated macaques, but the simultaneous appearance of CD8+ T cells with HEV clearance may support the role of this subset in controlling virus replication. However, virus clearance in the absence of CD8+ T cells indicates that neutralizing antibodies and/or CD4+ T cells may act autonomously to inhibit HEV replication.

JOURNAL OF HEPATOLOGY (2021)

Article Microbiology

A Cross-Species Transmission of a Camel-Derived Genotype 8 Hepatitis E Virus to Rabbits

Wenjing Zhang et al.

Summary: Novel genotypes of HEV have been identified in wild animals, with HEV-8 able to cross species and infect rabbits, while HEV-5 and HEV-7 cannot infect rabbits.

PATHOGENS (2021)

Review Infectious Diseases

Extrahepatic manifestations related to hepatitis E virus infection and their triggering mechanisms

Jian Wu et al.

Summary: Hepatitis E virus (HEV) infection has various extrahepatic manifestations affecting multiple organ systems, indicating it should be considered as a systemic disease. Different genotypes of HEV can induce different extrahepatic manifestations, and the severity of these diseases does not necessarily correlate with the severity of HEV infection. Antiviral therapy may alleviate or improve the extrahepatic manifestations related to HEV infection.

JOURNAL OF INFECTION (2021)

Article Virology

The Viral ORF3 Protein Is Required for Hepatitis E Virus Apical Release and Efficient Growth in Polarized Hepatocytes and Humanized Mice

Gulce Sari et al.

Summary: ORF3 plays a crucial role in HEV release and persistent infection, as its absence significantly decreases HEV replication and virion release. Our findings provide a rationale for targeting ORF3 as a treatment strategy for HEV infection.

JOURNAL OF VIROLOGY (2021)

Article Gastroenterology & Hepatology

Treatment induced clearance of hepatitis E viruses by interferon-lambda in liver-humanized mice

Gulce Sari et al.

Summary: PegIFN lambda is well tolerated in mice and leads to clearance of a persistent HEV infection in liver-humanized mice. The study found that human liver cells express the IFN lambda receptor and are responsive to pegIFN lambda. Dose escalation studies showed that a dose of 0.3 mg/kg pegIFN lambda treatment resulted in complete clearance of HEV antigen and HEV RNA from the liver in 8 out of 9 liver-humanized mice, demonstrating the potential efficacy of pegIFN lambda in treating chronic HEV infections.

LIVER INTERNATIONAL (2021)

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Hepatitis E viral infection causes testicular damage in mice

Jianwen Situ et al.

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Experimental infection of hepatitis E virus induces pancreatic necroptosis in miniature pigs

Soontag Jung et al.

SCIENTIFIC REPORTS (2020)

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Infectivity and pathogenicity of different hepatitis E virus genotypes/subtypes in rabbit model

Shuangshuang Li et al.

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Current status of hepatitis E virus infection at a rhesus monkey farm in China

Fengmei Yang et al.

VETERINARY MICROBIOLOGY (2019)

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Detection of hepatitis E virus antibodies among Cercopithecidae and Hominidae monkeys in Cameroon

Abdou Fatawou Modiyinji et al.

JOURNAL OF MEDICAL PRIMATOLOGY (2019)

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HEV-LFS: A novel scoring model for patients with hepatitis E virus-related liver failure

Jian Wu et al.

JOURNAL OF VIRAL HEPATITIS (2019)

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Hepatitis E Virus: Animal Models and Zoonosis

Scott P. Kenney et al.

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Genotype 5 Hepatitis E Virus Produced by a Reverse Genetics System Has the Potential for Zoonotic Infection

Tian-Cheng Li et al.

HEPATOLOGY COMMUNICATIONS (2019)

Article Pharmacology & Pharmacy

The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo

Daniel Todt et al.

ANTIVIRAL RESEARCH (2018)

Article Biochemistry & Molecular Biology

Evaluation of autophagy induction on HEV 239 vaccine immune response in a mouse model

Mehdi Khateri et al.

IUBMB LIFE (2018)

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Past, present and future of hepatitis E virus infection: Zoonotic perspectives

Shahid Faraz Syed et al.

MICROBIAL PATHOGENESIS (2018)

Article Microbiology

Cross-species infection of mice by rabbit hepatitis E virus

Yani Sun et al.

VETERINARY MICROBIOLOGY (2018)

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High sensitivity of domestic pigs to intravenous infection with HEV

Lisa Daehnert et al.

BMC VETERINARY RESEARCH (2018)

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No Evidence of Rat Hepatitis E Virus Excretion in Urine Samples of Rats

Tian-Cheng Li et al.

JAPANESE JOURNAL OF INFECTIOUS DISEASES (2017)

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Hepatitis E virus infection and acute non-traumatic neurological injury: A prospective multicentre study

Harry R. Dalton et al.

JOURNAL OF HEPATOLOGY (2017)

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Hepatitis E Virus Infects Neurons and Brains

Xinying Zhou et al.

JOURNAL OF INFECTIOUS DISEASES (2017)

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Prevalence and genetic features of rabbit hepatitis E virus in Korea

Hee-Seop Ahn et al.

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Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity

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Foodborne Transmission of Hepatitis E Virus from Raw Pork Liver Sausage, France

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New Hepatitis E Virus Genotype in Camels, the Middle East

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Susceptibility of laboratory rats against genotypes 1, 3, 4, and rat hepatitis E viruses

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Pathobiology of hepatitis E: lessons learned from primate models

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Characterization of Full Genome of Rat Hepatitis E Virus Strain from Vietnam

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Transmission of Hepatitis E Virus from Rabbits to Cynomolgus Macaques

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Asian Musk Shrew as a Reservoir of Rat Hepatitis E Virus, China

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Cross-species infection of pigs with a novel rabbit, but not rat, strain of hepatitis E virus isolated in the United States

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Rabbit as a Novel Animal Model for Hepatitis E Virus Infection and Vaccine Evaluation

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Detection of a novel hepatitis E-like virus in faeces of wild rats using a nested broad-spectrum RT-PCR

Reimar Johne et al.

JOURNAL OF GENERAL VIROLOGY (2010)

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Pig Liver Sausage as a Source of Hepatitis E Virus Transmission to Humans

Philippe Colson et al.

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Novel Hepatitis E Virus Genotype in Norway Rats, Germany

Reimar Johne et al.

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Experimental infection of Balb/c nude mice with Hepatitis E virus

Fen Huang et al.

BMC INFECTIOUS DISEASES (2009)

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A Novel Genotype of Hepatitis E Virus Prevalent Among Farmed Rabbits in China

Chenyan Zhao et al.

JOURNAL OF MEDICAL VIROLOGY (2009)

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Hepatitis E virus and chronic hepatitis in organ-transplant recipients.

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Type-IV Indian swine HEV infects rhesus monkeys

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JOURNAL OF VIRAL HEPATITIS (2006)

Letter Immunology

Severe hepatitis E virus infection after ingestion of uncooked liver from a wild boar

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JOURNAL OF INFECTIOUS DISEASES (2003)

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Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine model

TPE Williams et al.

JOURNAL OF CLINICAL MICROBIOLOGY (2001)