Experimental infection of rabbits with genotype 3 hepatitis E virus produced both chronicity and kidney injury

Wang, Lin; Xia, Jingyan; Wang, Youchun

doi:10.1136/gutjnl-2016-312023

Cited by 31 publications

(37 citation statements)

References 5 publications

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“…In this study, acute and chronic-type infections were observed in the two HEV8-infected monkeys. Protracted fecal shedding of HEV without viremia has been reported both in animals (25,27,32,33) and in chronic hepatitis E patients (34,35) and agrees well with the natural course of HEV infections (1). Although most chronic HEV infection cases occurred in immunocompromised patients, several studies have reported that occasionally, immunocompetent individuals can also develop chronic hepatitis E (36,37).…”

Section: Discussionsupporting

confidence: 75%

“…Although most chronic HEV infection cases occurred in immunocompromised patients, several studies have reported that occasionally, immunocompetent individuals can also develop chronic hepatitis E (36,37). In animal studies, chronic HEV infection has been established in healthy rabbits (33), rhesus monkeys (29), and ferrets (38). The underlying mechanisms responsible for the different disease profiles remain unclear, but the findings of this study provide a potential alternative animal model for more detailed study of chronic HEV infection.…”

Section: Discussionmentioning

confidence: 87%

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Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques

Wang

Teng

Lau

et al. 2019

J Virol

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Hepatitis E virus (HEV) is zoonotic and a major cause of acute viral hepatitis worldwide. Recently, we identified a novel HEV genotype 8 (HEV8) in Bactrian camels in Xinjiang, China. However, the epidemiology, pathogenicity, and zoonotic potential of HEV8 are unclear. Here, we present the prevalence of HEV8 in China and investigate its pathogenicity and cross-species transmission in cynomolgus macaques. Fresh fecal and milk samples from Bactrian camels collected from four provinces/regions in China were screened for HEV RNA by reverse transcriptase PCR (RT-PCR). An HEV8-positive sample was used to inoculate two cynomolgus macaques to examine the potential for cross-species infection. The pathogenicity of HEV8 was analyzed by testing HEV markers and liver function during the study period and histopathology of liver biopsy specimens at 3, 13, and 25 weeks postinoculation. Extrahepatic replication was tested by using reverse transcriptase quantitative PCR (RT-qPCR) and immunofluorescence assays. The overall prevalence of HEV8 RNA in Chinese Bactrian camels was 1.4% (4/295), and positive samples were found in three different provinces/regions in China. Histopathology confirmed acute and chronic HEV8 infections in the two monkeys. Multiple tissues were positive for HEV RNA and ORF2 proteins. Renal pathology was observed in the monkey with chronic hepatitis. Whole-genome sequencing showed only 1 to 3 mutations in the HEV8 in the fecal samples from the two monkeys compared to that from the camel. HEV8 is circulating in multiple regions in China. Infection of two monkeys with HEV8 induced chronic and systemic infections, demonstrating the high potential zoonotic risk of HEV8.IMPORTANCE It is estimated that one-third of the world population have been exposed to hepatitis E virus (HEV). In developed countries and China, zoonotic HEV strains are responsible for almost all acute and chronic HEV infection cases. It is always of immediate interest to investigate the zoonotic potential of novel HEV strains. In 2016, we discovered a novel HEV genotype, HEV8, in Bactrian camels, but the epidemiology, zoonotic potential, and pathogenicity of the virus were unknown. In the present study, we demonstrated that HEV8 was circulating in multiple regions in China and was capable of infecting cynomolgus macaques, a surrogate for humans, posing high risk of zoonosis. Chronic hepatitis, systemic infection, and renal pathology were observed. Collectively, these data indicate that HEV8 exhibits a high potential for zoonotic transmission. Considering the importance of Bactrian camels as livestock animals, risk groups, such as camelid meat and milk consumers, should be screened for HEV8 infection.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 87%

Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques

Wang

Teng

Lau

et al. 2019

J Virol

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“…Another advantage is that rabbits can be used to simulate the high mortality rate associated with pregnancy in humans [116]. Rabbits can even be used as a model of chronic infection with HEV3 and extra-hepatic manifestations [117]. …”

Section: Animal and In Vitro Modelsmentioning

confidence: 99%

Hepatitis E Pathogenesis

Lhomme

Marion

Abravanel

et al. 2016

Viruses

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“…The same observation has been reported in human, too, and it may be related to the compromised host immune status. In a further investigation, inocula with 10 4 , 10 5 , and 10 6 copies of CHN‐BJ‐rb14 were, respectively, injected i.v. into 2 naïve SPF rabbits, and rabbits inoculated with 10 6 copies of rHEV subsequently developed persistent infection of HEV.…”

Section: Pathogenesis Of Rhevmentioning

confidence: 99%

An overview: Rabbit hepatitis E virus (HEV) and rabbit providing an animal model for HEV study

Wang

Liu

2017

Reviews in Medical Virology

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SummaryHepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus and the causative agent of hepatitis E. The virus belongs to genus Orthohepevirus in the family Hepeviridae, which contains 4 major genotypes closely relating to humans. Genotypes 1 and 2 only infect humans whereas genotypes 3 and 4 HEV are harbored in a wide range of animal species worldwide and are zoonotic to humans. Recently, a novel animal strain of HEV has been isolated in farmed rabbits in China, and subsequently more strains were discovered in the rabbit populations in at least 7 other countries. Due to high sequence similarity to genotype 3 HEV, rabbit HEV (rHEV) has been assigned to genotype 3. Experimental study showed that rHEV could infect non-human primate and human, which pose a direct threat to human. Further pathogenesis studies showed laboratory rabbits infected with rHEV and genotype 4 HEV could present similar signs of acute and chronic hepatitis E along with extra-hepatic replication as observed in humans. High mortality and vertical transmission were reproduced in rHEV infected pregnant rabbits. Furthermore, rabbit model was also found suitable for evaluating HEV vaccine efficacy in order to manage zoonotic transmission. These data showed laboratory rabbits could serve as an alternative animal model for HEV study under the current circumstances that HEV propagation is limited in vitro. In general, this review aims at presenting comprehensive up-to-date information about rHEV strains and rabbit model for HEV studies.

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Experimental infection of rabbits with genotype 3 hepatitis E virus produced both chronicity and kidney injury

Cited by 31 publications

References 5 publications

Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques

Transmission of a Novel Genotype of Hepatitis E Virus from Bactrian Camels to Cynomolgus Macaques

Hepatitis E Pathogenesis

An overview: Rabbit hepatitis E virus (HEV) and rabbit providing an animal model for HEV study

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