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Article: Multimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy

TitleMultimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy
Authors
Keywordshepatitis E
rat hepatitis E
HEV-C1
zoonosis
viral hepatitis
Issue Date2021
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep
Citation
Journal of Hepatology, 2021, v. 74 n. 6, p. 1315-1324 How to Cite?
AbstractBackground & Aims: Rat hepatitis E virus (Orthohepevirus species C; HEV-C1) is an emerging cause of viral hepatitis in humans. HEV-C1 is divergent from other HEV variants infecting humans that belong to Orthohepevirus species A (HEV-A). This study assessed HEV-C1 antigenic divergence from HEV-A and investigated the impact of this divergence on infection susceptibility, serological test sensitivity, and vaccine efficacy. Methods: Immunodominant E2s peptide sequences of HEV-A and HEV-C1 were aligned. Interactions of HEV-C1 E2s and anti-HEV-A monoclonal antibodies (mAbs) were modeled. Recombinant peptides incorporating E2s of HEV-A (HEV-A4 p239) and HEV-C1 (HEV-C1 p241) were expressed. HEV-A and HEV-C1 patient sera were tested using antibody enzymatic immunoassays (EIA), antigen EIAs, and HEV-A4 p239/HEV-C1 p241 immunoblots. Rats immunized with HEV-A1 p239 vaccine (Hecolin), HEV-A4 p239 or HEV-C1 p241 peptides were challenged with a HEV-C1 strain. Results: E2s sequence identity between HEV-A and HEV-C1 was only 48%. There was low conservation at E2s residues (23/53; 43.4%) involved in mAb binding. Anti-HEV-A mAbs bound HEV-C1 poorly in homology modeling and antigen EIAs. Divergence resulted in low sensitivity of commercial antigen (0%) and antibody EIAs (10–70%) for HEV-C1 diagnosis. Species-specific HEV-A4 p239/HEV-C1 p241 immunoblots accurately differentiated HEV-A and HEV-C1 serological profiles in immunized rats (18/18; 100%) and infected-patient sera (32/36; 88.9%). Immunization with Hecolin and HEV-A4 p239 was partially protective while HEV-C1 p241 was fully protective against HEV-C1 infection in rats. Conclusions: Antigenic divergence significantly decreases sensitivity of hepatitis E serodiagnostic assays for HEV-C1 infection. Species-specific immunoblots are useful for diagnosing HEV-C1 and for differentiating the serological profiles of HEV-A and HEV-C1. Prior HEV-A exposure is not protective against HEV-C1. HEV-C1 p241 is an immunogenic vaccine candidate against HEV-C1. Lay summary: Rat hepatitis E virus (HEV-C1) is a new cause of hepatitis in humans. Using a combination of methods, we showed that HEV-C1 is highly divergent from the usual cause of human hepatitis (HEV-A). This divergence reduces the capacity of existing tests to diagnose HEV-C1 and also indicates that prior exposure to HEV-A (via infection or vaccination) is not protective against HEV-C1.
Persistent Identifierhttp://hdl.handle.net/10722/304711
ISSN
2023 Impact Factor: 26.8
2023 SCImago Journal Rankings: 9.857
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSridhar, S-
dc.contributor.authorSitu, J-
dc.contributor.authorCai, JP-
dc.contributor.authorYip, CCY-
dc.contributor.authorWu, S-
dc.contributor.authorZhang, AJX-
dc.contributor.authorWen, L-
dc.contributor.authorChew, NFS-
dc.contributor.authorChan, WM-
dc.contributor.authorPoon, RWS-
dc.contributor.authorChan, JFW-
dc.contributor.authorTsang, DNC-
dc.contributor.authorChen, H-
dc.contributor.authorXia, NS-
dc.contributor.authorYuen, KY-
dc.date.accessioned2021-10-05T02:34:03Z-
dc.date.available2021-10-05T02:34:03Z-
dc.date.issued2021-
dc.identifier.citationJournal of Hepatology, 2021, v. 74 n. 6, p. 1315-1324-
dc.identifier.issn0168-8278-
dc.identifier.urihttp://hdl.handle.net/10722/304711-
dc.description.abstractBackground & Aims: Rat hepatitis E virus (Orthohepevirus species C; HEV-C1) is an emerging cause of viral hepatitis in humans. HEV-C1 is divergent from other HEV variants infecting humans that belong to Orthohepevirus species A (HEV-A). This study assessed HEV-C1 antigenic divergence from HEV-A and investigated the impact of this divergence on infection susceptibility, serological test sensitivity, and vaccine efficacy. Methods: Immunodominant E2s peptide sequences of HEV-A and HEV-C1 were aligned. Interactions of HEV-C1 E2s and anti-HEV-A monoclonal antibodies (mAbs) were modeled. Recombinant peptides incorporating E2s of HEV-A (HEV-A4 p239) and HEV-C1 (HEV-C1 p241) were expressed. HEV-A and HEV-C1 patient sera were tested using antibody enzymatic immunoassays (EIA), antigen EIAs, and HEV-A4 p239/HEV-C1 p241 immunoblots. Rats immunized with HEV-A1 p239 vaccine (Hecolin), HEV-A4 p239 or HEV-C1 p241 peptides were challenged with a HEV-C1 strain. Results: E2s sequence identity between HEV-A and HEV-C1 was only 48%. There was low conservation at E2s residues (23/53; 43.4%) involved in mAb binding. Anti-HEV-A mAbs bound HEV-C1 poorly in homology modeling and antigen EIAs. Divergence resulted in low sensitivity of commercial antigen (0%) and antibody EIAs (10–70%) for HEV-C1 diagnosis. Species-specific HEV-A4 p239/HEV-C1 p241 immunoblots accurately differentiated HEV-A and HEV-C1 serological profiles in immunized rats (18/18; 100%) and infected-patient sera (32/36; 88.9%). Immunization with Hecolin and HEV-A4 p239 was partially protective while HEV-C1 p241 was fully protective against HEV-C1 infection in rats. Conclusions: Antigenic divergence significantly decreases sensitivity of hepatitis E serodiagnostic assays for HEV-C1 infection. Species-specific immunoblots are useful for diagnosing HEV-C1 and for differentiating the serological profiles of HEV-A and HEV-C1. Prior HEV-A exposure is not protective against HEV-C1. HEV-C1 p241 is an immunogenic vaccine candidate against HEV-C1. Lay summary: Rat hepatitis E virus (HEV-C1) is a new cause of hepatitis in humans. Using a combination of methods, we showed that HEV-C1 is highly divergent from the usual cause of human hepatitis (HEV-A). This divergence reduces the capacity of existing tests to diagnose HEV-C1 and also indicates that prior exposure to HEV-A (via infection or vaccination) is not protective against HEV-C1.-
dc.languageeng-
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/jhep-
dc.relation.ispartofJournal of Hepatology-
dc.subjecthepatitis E-
dc.subjectrat hepatitis E-
dc.subjectHEV-C1-
dc.subjectzoonosis-
dc.subjectviral hepatitis-
dc.titleMultimodal investigation of rat hepatitis E virus antigenicity: Implications for infection, diagnostics, and vaccine efficacy-
dc.typeArticle-
dc.identifier.emailSridhar, S: sid8998@hku.hk-
dc.identifier.emailSitu, J: situjw@hku.hk-
dc.identifier.emailCai, JP: caijuice@hku.hk-
dc.identifier.emailYip, CCY: yipcyril@hku.hk-
dc.identifier.emailWu, S: wss2017@hku.hk-
dc.identifier.emailZhang, AJX: zhangajx@hkucc.hku.hk-
dc.identifier.emailChew, NFS: chewnf@hku.hk-
dc.identifier.emailChan, WM: mbally@hku.hk-
dc.identifier.emailPoon, RWS: rosana@hkucc.hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailChen, H: hlchen@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authoritySridhar, S=rp02249-
dc.identifier.authorityYip, CCY=rp01721-
dc.identifier.authorityZhang, AJX=rp00413-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityChen, H=rp00383-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.jhep.2020.12.028-
dc.identifier.pmid33845058-
dc.identifier.scopuseid_2-s2.0-85105354910-
dc.identifier.hkuros325982-
dc.identifier.volume74-
dc.identifier.issue6-
dc.identifier.spage1315-
dc.identifier.epage1324-
dc.identifier.isiWOS:000654740300007-
dc.publisher.placeNetherlands-

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