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      Redeveloping antigen detection kits for the diagnosis of rat hepatitis E virus

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          ABSTRACT

          The emergence of Rocahepevirus ratti [species HEV ratti ( r HEV)] as a causative agent of hepatitis E in humans presents a new potential threat to global public health. The R. ratti genotype 1 ( r-1 HEV) variant only shares 50%–60% genomic identity with Paslahepevirus balayani [species HEV balayani ( b HEV)] variants, which are the main causes of hepatitis E infection in humans. Here, we report antigen diagnoses for r-1 HEV and b HEV using an enzymatic immunoassay (EIA) method. We detected recombinant virus-like particles protein (HEV 239) of r HEV and b HEV using a collection of hepatitis E virus (HEV)-specific monoclonal antibodies. Two optimal candidates, the capture antibody P#1-H4 and the detection antibodies C145 (P#1-H4*/C145 #) and C158 (P#1-H4*/C158 #), were selected to detect antigen in infected rat samples and r-1 HEV- or b HEV-infected human clinical samples. The two candidates showed similar diagnostic efficacy to the Wantai HEV antigen kit in b HEV-infected clinical samples. Genomic divergence resulted in low diagnostic efficacy of the Wantai HEV antigen kit (0%, 0 of 10) for detecting r-1 HEV infection. Compared with the P#1-H4*/C145 # candidate (80%, 8 of 10), the P#1-H4*/C158 # candidate had excellent diagnostic efficacy in r-1 HEV-infected clinical samples (100%, 10 of 10). The two candidates bind to a discrete antigenic site that is highly conserved across r HEV and b HEV. P#1-H4*/C145 # and P#1-H4*/C158 # are efficacious candidate antibody combinations for rat HEV antigen detection.

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          Chronic Infection With Camelid Hepatitis E Virus in a Liver Transplant Recipient Who Regularly Consumes Camel Meat and Milk.

          There have been increasing reports of food-borne zoonotic transmission of hepatitis E virus (HEV) genotype 3, which causes chronic infections in immunosuppressed patients. We performed phylogenetic analyses of the HEV sequence (partial and full-length) from 1 patient from the Middle East who underwent liver transplantation, and compared it with other orthohepevirus A sequences. We found the patient to be infected by camelid HEV. This patient regularly consumed camel meat and milk, therefore camelid HEV, which is genotype 7, might infect human beings. Our finding links consumption of camel-derived food products to post-transplantation hepatitis E, which, if detected at early stages, can be cured with antiviral therapy and reduced administration of immunosuppressive agents.
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            Hepatitis E virus infection

            Hepatitis E virus (HEV) infection can lead to acute and chronic hepatitis as well as to extrahepatic manifestations such as neurological and renal disease; it is the most common cause of acute viral hepatitis worldwide. Four genotypes are responsible for most infection in humans, of which HEV genotypes 1 and 2 are obligate human pathogens and HEV genotypes 3 and 4 are mostly zoonotic. Until quite recently, HEV was considered to be mainly responsible for epidemics of acute hepatitis in developing regions owing to contamination of drinking water supplies with human faeces. However, HEV is increasingly being recognized as endemic in some developed regions. In this setting, infections occur through zoonotic transmission or contaminated blood products and can cause chronic hepatitis in immunocompromised individuals. HEV infections can be diagnosed by measuring anti-HEV antibodies, HEV RNA or viral capsid antigen in blood or stool. Although an effective HEV vaccine exists, it is only licensed for use in China. Acute hepatitis E is usually self-limiting and does not require specific treatment. Management of immunocompromised individuals involves lowering the dose of immunosuppressive drugs and/or treatment with the antiviral agent ribavirin.
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              Hepatitis E Virus Genotypes and Evolution: Emergence of Camel Hepatitis E Variants

              Hepatitis E virus (HEV) is a major cause of viral hepatitis globally. Zoonotic HEV is an important cause of chronic hepatitis in immunocompromised patients. The rapid identification of novel HEV variants and accumulating sequence information has prompted significant changes in taxonomy of the family Hepeviridae. This family includes two genera: Orthohepevirus, which infects terrestrial vertebrates, and Piscihepevirus, which infects fish. Within Orthohepevirus, there are four species, A–D, with widely differing host range. Orthohepevirus A contains the HEV variants infecting humans and its significance continues to expand with new clinical information. We now recognize eight genotypes within Orthohepevirus A: HEV1 and HEV2, restricted to humans; HEV3, which circulates among humans, swine, rabbits, deer and mongooses; HEV4, which circulates between humans and swine; HEV5 and HEV6, which are found in wild boars; and HEV7 and HEV8, which were recently identified in dromedary and Bactrian camels, respectively. HEV7 is an example of a novel genotype that was found to have significance to human health shortly after discovery. In this review, we summarize recent developments in HEV molecular taxonomy, epidemiology and evolution and describe the discovery of novel camel HEV genotypes as an illustrative example of the changes in this field.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: Writing – original draftRole: Writing – review and editing
                Role: Data curationRole: Investigation
                Role: ConceptualizationRole: Formal analysisRole: Investigation
                Role: InvestigationRole: Resources
                Role: Data curation
                Role: Resources
                Role: Funding acquisitionRole: Resources
                Role: Funding acquisitionRole: Resources
                Role: Validation
                Role: Resources
                Role: Resources
                Role: Resources
                Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: Writing – review and editing
                Role: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: Writing – review and editing
                Role: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: Resources
                Role: Editor
                Journal
                J Clin Microbiol
                J Clin Microbiol
                jcm
                Journal of Clinical Microbiology
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                0095-1137
                1098-660X
                December 2023
                01 December 2023
                01 December 2023
                : 61
                : 12
                : e00710-23
                Affiliations
                [1 ] State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Department of Laboratory Medicine, School of Public Health, Xiamen University; , Xiamen, Fujian, China
                [2 ] National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, School of Public Health, School of Life Sciences, Xiamen University; , Xiamen, Fujian, China
                [3 ] Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong; , Pokfulam, Hong Kong, China
                [4 ] The First Affiliated Hospital of Xiamen University, Xiamen University; , Xiamen, Fujian, China
                [5 ] United Diagnostic and Research Center for Clinical Genetics, Women and Children’s Hospital, School of Medicine & School of Public Health, Xiamen University; , Xiamen, Fujian, China
                [6 ] State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong; , Hong Kong, China
                [7 ] Carol Yu Centre for Infection, The University of Hong Kong; , Hong Kong, China
                [8 ] Research Unit of Frontier Technology of Structural Vaccinology, Chinese Academy of Medical Sciences; , Xiamen, Fujian, China
                Boston Children's Hospital; , Boston, Massachusetts, USA
                Author notes
                Address correspondence to Siddharth Sridhar, sid8998@ 123456hku.hk
                Address correspondence to Zizheng Zheng, zhengzizheng@ 123456xmu.edu.cn

                Zihao Chen, Guanghui Li, Jianwen Situ, and Zhiyong Li contributed equally to this article. Author order was determined on the basis of seniority.

                The authors declare no conflict of interest.

                Author information
                https://orcid.org/0000-0002-8221-0751
                https://orcid.org/0000-0002-2022-8307
                https://orcid.org/0000-0003-0099-4212
                Article
                00710-23 jcm.00710-23
                10.1128/jcm.00710-23
                10729709
                38038482
                988eb399-da71-4148-9bfe-754d737b8e24
                Copyright © 2023 Chen et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 03 June 2023
                : 07 October 2023
                Page count
                supplementary-material: 1, authors: 16, Figures: 6, Tables: 2, References: 37, Pages: 15, Words: 8514
                Funding
                Funded by: The National Natural Science Foundation of China;
                Award ID: 82071783, 82171746, 82001757
                Award Recipient :
                Funded by: The Natural Science Foundation of Fujian Province;
                Award ID: 2022J02005
                Award Recipient :
                Funded by: The Major Science and Technology Project for Significant New Drugs Ceration;
                Award ID: 2018ZX09303005-002
                Award Recipient :
                Funded by: The CAMS Innovation Fund for Medical Sciences;
                Award ID: 2019RU022
                Award Recipient :
                Funded by: Fundamental Research Funds for Medical Sciences;
                Award ID: 20720220006
                Award Recipient :
                Funded by: The Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region;
                Award ID: 19180442
                Award Recipient :
                Funded by: The HKUMed Research Fellowship Scheme for Clinical Academics;
                Award ID: 2022-23
                Award Recipient :
                Funded by: Hong Kong Research Grants Council under Early Career Scheme;
                Award ID: 27107420
                Award Recipient :
                Categories
                Clinical Veterinary Microbiology
                clinical-microbiology, Clinical Microbiology
                Custom metadata
                December 2023

                Microbiology & Virology
                rocahepevirus ratti,paslahepevirus balayani,rat hepatitis e virus,antigen diagnosis

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