An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humans
Background & Aims: Rat hepatitis E virus (Rocahepevirus ratti; HEV-C1) is an emerging cause of hepatitis E that is divergent from conventional human-infecting HEV variants (Paslahepevirus balayani; HEV-A). Validated serological assays for HEV-C1 are lacking. We aimed to develop a parallel en...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
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| Series: | JHEP Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555923001246 |
| _version_ | 1827856070042714112 |
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| author | Jianwen Situ Kelvin Hon-Yin Lo Jian-Piao Cai Zhiyu Li Shusheng Wu Estie Hon-Kiu Shun Nicholas Foo-Siong Chew James Yiu-Hung Tsoi Gabriel Sze-Man Chan Winson Hei-Man Chan Cyril Chik-Yan Yip Kong Hung Sze Vincent Chi-Chung Cheng Kwok-Yung Yuen Siddharth Sridhar |
| author_facet | Jianwen Situ Kelvin Hon-Yin Lo Jian-Piao Cai Zhiyu Li Shusheng Wu Estie Hon-Kiu Shun Nicholas Foo-Siong Chew James Yiu-Hung Tsoi Gabriel Sze-Man Chan Winson Hei-Man Chan Cyril Chik-Yan Yip Kong Hung Sze Vincent Chi-Chung Cheng Kwok-Yung Yuen Siddharth Sridhar |
| author_sort | Jianwen Situ |
| collection | DOAJ |
| description | Background & Aims: Rat hepatitis E virus (Rocahepevirus ratti; HEV-C1) is an emerging cause of hepatitis E that is divergent from conventional human-infecting HEV variants (Paslahepevirus balayani; HEV-A). Validated serological assays for HEV-C1 are lacking. We aimed to develop a parallel enzymatic immunoassay (EIA) system that identifies individuals with HEV-C1 exposure. We also aimed to conduct the first HEV-C1 seroprevalence study in humans using this validated EIA system. Methods: Expressed HEV-A (HEV-A4 p239) and HEV-C1 (HEV-C1 p241) peptides were characterised. Blood samples were simultaneously tested in HEV-A4 p239 and HEV-C1 p241 IgG EIAs. An optical density (OD) cut-off-based interpretation algorithm for identifying samples seropositive for HEV-A or HEV-C1 was validated using RT-PCR-positive infection sera. This algorithm was used to measure HEV-C1 seroprevalence in 599 solid organ transplant recipients and 599 age-matched immunocompetent individuals. Results: Both peptides formed virus-like particles. When run in HEV-A4 p239 and HEV-C1 p241 EIAs, HEV-A and HEV-C1 RT-PCR-positive samples formed distinct clusters with minimal overlap in a two-dimensional plot of optical density values. The final EIA interpretation algorithm showed high agreement with RT-PCR results (Cohen’s κ = 0.959) and was able to differentiate HEV-A and HEV-C1 infection sera with an accuracy of 94.2% (95% CI: 85.8–98.4%). HEV-C1 IgG seroprevalence was 7/599 (1.2%) among solid organ transplant recipients and 4/599 (0.7%) among immunocompetent individuals. Five of 11 (45.5%) of these patients had history of transient hepatitis of unknown cause. Conclusions: HEV-C1 exposure was identified in 11/1198 (0.92%) individuals in Hong Kong indicating endemic exposure. This is the first estimate of HEV-C1 seroprevalence in humans. The parallel IgG EIA algorithm is a valuable tool for investigating epidemiology and risk factors for HEV-C1 infection. Impact and Implications: Rat hepatitis E virus has recently been discovered to infect humans, but antibody tests for this infection are lacking, making it difficult to gauge how common this infection is. We developed an antibody test algorithm that can identify individuals with past rat hepatitis E virus exposure. We used this algorithm to estimate rat hepatitis E exposure rates in humans in Hong Kong and found that approximately 1% of all tested people had been exposed to this virus previously. |
| first_indexed | 2024-03-12T12:19:28Z |
| format | Article |
| id | doaj.art-3635aeb2b2d241e78fa7847b44c46c90 |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-03-12T12:19:28Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-3635aeb2b2d241e78fa7847b44c46c902023-08-30T05:54:38ZengElsevierJHEP Reports2589-55592023-09-0159100793An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humansJianwen Situ0Kelvin Hon-Yin Lo1Jian-Piao Cai2Zhiyu Li3Shusheng Wu4Estie Hon-Kiu Shun5Nicholas Foo-Siong Chew6James Yiu-Hung Tsoi7Gabriel Sze-Man Chan8Winson Hei-Man Chan9Cyril Chik-Yan Yip10Kong Hung Sze11Vincent Chi-Chung Cheng12Kwok-Yung Yuen13Siddharth Sridhar14Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China; Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China; The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong, China; Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, Hong Kong, ChinaDepartment of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China; Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China; Corresponding author. Address: Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China. Tel.: +00-852-22552408; fax: +00-852-28551241.Background & Aims: Rat hepatitis E virus (Rocahepevirus ratti; HEV-C1) is an emerging cause of hepatitis E that is divergent from conventional human-infecting HEV variants (Paslahepevirus balayani; HEV-A). Validated serological assays for HEV-C1 are lacking. We aimed to develop a parallel enzymatic immunoassay (EIA) system that identifies individuals with HEV-C1 exposure. We also aimed to conduct the first HEV-C1 seroprevalence study in humans using this validated EIA system. Methods: Expressed HEV-A (HEV-A4 p239) and HEV-C1 (HEV-C1 p241) peptides were characterised. Blood samples were simultaneously tested in HEV-A4 p239 and HEV-C1 p241 IgG EIAs. An optical density (OD) cut-off-based interpretation algorithm for identifying samples seropositive for HEV-A or HEV-C1 was validated using RT-PCR-positive infection sera. This algorithm was used to measure HEV-C1 seroprevalence in 599 solid organ transplant recipients and 599 age-matched immunocompetent individuals. Results: Both peptides formed virus-like particles. When run in HEV-A4 p239 and HEV-C1 p241 EIAs, HEV-A and HEV-C1 RT-PCR-positive samples formed distinct clusters with minimal overlap in a two-dimensional plot of optical density values. The final EIA interpretation algorithm showed high agreement with RT-PCR results (Cohen’s κ = 0.959) and was able to differentiate HEV-A and HEV-C1 infection sera with an accuracy of 94.2% (95% CI: 85.8–98.4%). HEV-C1 IgG seroprevalence was 7/599 (1.2%) among solid organ transplant recipients and 4/599 (0.7%) among immunocompetent individuals. Five of 11 (45.5%) of these patients had history of transient hepatitis of unknown cause. Conclusions: HEV-C1 exposure was identified in 11/1198 (0.92%) individuals in Hong Kong indicating endemic exposure. This is the first estimate of HEV-C1 seroprevalence in humans. The parallel IgG EIA algorithm is a valuable tool for investigating epidemiology and risk factors for HEV-C1 infection. Impact and Implications: Rat hepatitis E virus has recently been discovered to infect humans, but antibody tests for this infection are lacking, making it difficult to gauge how common this infection is. We developed an antibody test algorithm that can identify individuals with past rat hepatitis E virus exposure. We used this algorithm to estimate rat hepatitis E exposure rates in humans in Hong Kong and found that approximately 1% of all tested people had been exposed to this virus previously.http://www.sciencedirect.com/science/article/pii/S2589555923001246HEV-C1Orthohepevirus species CRocahepevirus rattiSeroepidemiologyAntibody assayVLP |
| spellingShingle | Jianwen Situ Kelvin Hon-Yin Lo Jian-Piao Cai Zhiyu Li Shusheng Wu Estie Hon-Kiu Shun Nicholas Foo-Siong Chew James Yiu-Hung Tsoi Gabriel Sze-Man Chan Winson Hei-Man Chan Cyril Chik-Yan Yip Kong Hung Sze Vincent Chi-Chung Cheng Kwok-Yung Yuen Siddharth Sridhar An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humans JHEP Reports HEV-C1 Orthohepevirus species C Rocahepevirus ratti Seroepidemiology Antibody assay VLP |
| title | An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humans |
| title_full | An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humans |
| title_fullStr | An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humans |
| title_full_unstemmed | An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humans |
| title_short | An immunoassay system to investigate epidemiology of Rocahepevirus ratti (rat hepatitis E virus) infection in humans |
| title_sort | immunoassay system to investigate epidemiology of rocahepevirus ratti rat hepatitis e virus infection in humans |
| topic | HEV-C1 Orthohepevirus species C Rocahepevirus ratti Seroepidemiology Antibody assay VLP |
| url | http://www.sciencedirect.com/science/article/pii/S2589555923001246 |
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