An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humans

Situ, Jianwen; Lo, Kelvin Hon-Yin; Cai, Jian‐Piao; Li, Zhiyu; Wu, Shusheng; Shun, Estie Hon-Kiu; Chew, Nicholas Foo-Siong; Tsoi, Jennifer; Chan, Godfrey C. F.; Chan, Wai-Chi; Yip, Cyril Chik-Yan; Sze, Kong Hung; Cheng, Vincent Chi-Chung; Yuen, Kwok‐Yung; Sridhar, Siddharth

doi:10.1016/j.jhepr.2023.100793

Cited by 9 publications

(11 citation statements)

References 23 publications

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“…HEV-A4-P239 and HEV-C1-P241 peptides were used to coat bHEV and rHEV EIA plates respectively. We have previously demonstrated that this EIA system is capable of differentiating bHEV and rHEV antibody signatures in human sera [ 17 ]. To investigate performance of these EIAs using dog or cat serum matrices, we spiked serially diluted IgG isolated from plasma of bHEV and rHEV positive patients into pools of 10 dog or cat sera that produced near-blank level ODs in a pilot evaluation in both bHEV and rHEV EIAs.…”

Section: Resultsmentioning

confidence: 99%

“…The genus Rocahepevirus was considered restricted to rodents, ferrets, and shrews. However, since 2018, we have reported endemic rHEV transmission in humans in Hong Kong with population seroprevalence indicating low-level endemicity [ 10 , 17 ]. Therefore, the distribution of Rocahepevirus variants in animals may be underestimated.…”

Section: Discussionmentioning

confidence: 99%

“…The in-house EIAs were coated with HEV-A4-P239 (0.5 μg/mL) or HEV-C1-P241 (0.5 μg/mL) in the solid phase to produce bHEV and rHEV EIA plates respectively [ 17 ]. We have previously shown good performance of this assay system in differentiating acute bHEV and rHEV infection in human patient sera (supplementary table 2).…”

Section: Methodsmentioning

confidence: 99%

“…However, these studies are often hampered by reliance on bHEV-based RT–PCR or antibody assays that either miss or cannot differentiate animals with rHEV exposure. In this study, we probed bHEV and rHEV seroprevalence in cats and dogs using specific quantitative real-time reverse transcription PCR (RT-qPCR) assays and an enzymatic immunoassay (EIA) system that is validated to detect and differentiate bHEV and rHEV antibody signatures in sera [ 17 ]. We have previously used this EIA system to report on rHEV seroprevalence in humans [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we probed bHEV and rHEV seroprevalence in cats and dogs using specific quantitative real-time reverse transcription PCR (RT-qPCR) assays and an enzymatic immunoassay (EIA) system that is validated to detect and differentiate bHEV and rHEV antibody signatures in sera [ 17 ]. We have previously used this EIA system to report on rHEV seroprevalence in humans [ 17 ]. We aimed to investigate sero-reactivity in cats and dogs to rHEV infection and measure species-specific HEV exposure rates in these animals.…”

Section: Introductionmentioning

confidence: 99%

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Rat hepatitis E virus (Rocahepevirus ratti) exposure in cats and dogs, Hong Kong

Shun,

Situ,

Tsoi

et al. 2024

Emerging Microbes & Infections

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Hepatitis E virus (HEV) variants infecting humans belong to two species: Paslahepevirus balayani (bHEV) and Rocahepevirus ratti (rat hepatitis E virus; rHEV). R. ratti is a ubiquitous rodent pathogen that has recently been recognized to cause hepatitis in humans. Transmission routes of rHEV from rats to humans are currently unknown. In this study, we examined rHEV exposure in cats and dogs to determine if they are potential reservoirs of this emerging human pathogen. Virus-like particle-based IgG enzymatic immunoassays (EIAs) capable of differentiating rHEV & bHEV antibody profiles and rHEV-specific real-time RT–PCR assays were used for this purpose. The EIAs could detect bHEV and rHEV patient-derived IgG spiked in dog and cat sera. Sera from 751 companion dogs and 130 companion cats in Hong Kong were tested with these IgG enzymatic immunoassays (EIAs). Overall, 13/751 (1.7%) dogs and 5/130 (3.8%) cats were sero-reactive to HEV. 9/751 (1.2%) dogs and 2/130 (1.5%) cats tested positive for rHEV IgG, which was further confirmed by rHEV immunoblots. Most rHEV-seropositive animals were from areas in or adjacent to districts reporting human rHEV infection. Neither 881 companion animals nor 652 stray animals carried rHEV RNA in serum or rectal swabs. Therefore, we could not confirm a role for cats and dogs in transmitting rHEV to humans. Further work is required to understand the reasons for low-level seropositivity in these animals.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rat hepatitis E virus (Rocahepevirus ratti) exposure in cats and dogs, Hong Kong

Shun,

Situ,

Tsoi

et al. 2024

Emerging Microbes & Infections

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Cell binding tropism of rat hepatitis E virus is a pivotal determinant of its zoonotic transmission to humans

Guo,

Xu,

Situ

et al. 2024

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

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Classically, all hepatitis E virus (HEV) variants causing human infection belong to the genus Paslahepevirus (HEV-A). However, the increasing cases of rat HEV infection in humans since 2018 challenged this dogma, posing increasing health threats. Herein, we investigated the underlying mechanisms dictating the zoonotic potentials of different HEV species and their possible cross-protection relationships. We found that rat HEV virus-like particles (HEV VLPs ) bound to human liver and intestinal cells/tissues with high efficiency. Moreover, rat HEV VLPs and infectious rat HEV particles penetrated the cell membrane and entered human target cells postbinding. In contrast, ferret HEV VLPs showed marginal cell binding and entry ability, bat HEV VLPs and avian HEV VLPs exhibited no binding and entry potency. Structure-based three-dimensional mapping identified that the surface spike domain of rat HEV is crucial for cell binding. Antigenic cartography indicated that rat HEV exhibited partial cross-reaction with HEV-A. Intriguingly, sera of HEV-A infected patients or human HEV vaccine Hecolin® immunized individuals provided partial cross-protection against the binding of rat HEV VLPs to human target cells. In summary, the interactions between the viral capsid and cellular receptor(s) regulate the distinct zoonotic potentials of different HEV species. The systematic characterization of antigenic cartography and serological cross-reactivity of different HEV species provide valuable insights for the development of species-specific diagnosis and protective vaccines against zoonotic HEV infection.

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Rat hepatitis E virus ( Rocahepevirus ratti ) in people living with HIV

Casares-Jimenez,

Rivero-Juarez,

Lopez-Lopez

et al. 2023

Emerging Microbes & Infections

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Rat hepatitis E virus (ratHEV; species Rocahepevirus ratti ) is considered a newly emerging cause of acute hepatitis of zoonotic origin. ratHEV infection of people living with HIV (PLWH) might portend a worse, as with hepatitis E virus (HEV; species Paslahepevirus balayani ), and consequently this group may constitute a high-risk population. We aimed to evaluate the prevalence of ratHEV by measuring viral RNA and specific IgG antibodies in a large Spanish cohort of PLWH. Multicentre study conducted in Spain evaluating PLWHIV included in the Spanish AIDS Research Network (CoRIS). Patients were evaluated for ratHEV infection using PCR at baseline and anti-ratHEV IgG by dot blot analysis to evaluate exposure to ratHEV strains. Patients with detectable ratHEV RNA were followed-up to evaluate persistence of viremia and IgG seroconversion. Eight-hundred and forty-two individuals were tested. A total of 9 individuals showed specific IgG antibodies against ratHEV, supposing a prevalence of 1.1 (95% CI; 0.5%−2.1%). Of these, only one was reactive to HEV IgG antibodies by ELISA. One sample was positive for ratHEV RNA (prevalence of infection: 0.1%; 95% CI: 0.08%−0.7%). The case was a man who had sex with men exhibiting a slightly increased alanine transaminase level (49 IU/L) as only biochemical alteration. In the follow-up, the patients showed undetectable ratHEV RNA and seroconversion to specific ratHEV IgG antibodies. Our study shows that ratHEV is geographical broadly distributed in Spain, representing a potential zoonotic threat.

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An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humans

Cited by 9 publications

References 23 publications

Rat hepatitis E virus (Rocahepevirus ratti) exposure in cats and dogs, Hong Kong

Rat hepatitis E virus (Rocahepevirus ratti) exposure in cats and dogs, Hong Kong

Cell binding tropism of rat hepatitis E virus is a pivotal determinant of its zoonotic transmission to humans

Rat hepatitis E virus ( Rocahepevirus ratti ) in people living with HIV

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