PhIP-Seq reveals geography- and disease-associated human herpesvirus antibody repertoires and distinct EBV response modules
Epstein-Barr virus (EBV) has been implicated in immune-mediated inflammatory diseases, but herpesvirus-directed humoral responses across populations and disease states remain incompletely defined. We profiled antibodies to all nine human herpesviruses by PhIP-Seq in 908 serum samples from 848 individuals in Madagascar and Germany. Cohorts showed distinct reactivity patterns, including cross-virus associations between homologous alphaherpesvirus envelope glycoproteins. German cohorts recognized a broader range of latent and lytic EBV proteins than Malagasy controls, with increased reactivity in primary sclerosing cholangitis. Proteome-wide profiling detected reactivity to 60 of 79 EBV proteins; 29 contained at least one peptide recognized in >5% of participants. Co-occurrence analyses identified an EBNA2–EBNA3A/B/C module and BFRF3–EBNA1 and BZLF1–BMRF1 pairs in German cohorts. Peptide ELISA showed individual-level concordance with PhIP-Seq for EBNA1. These findings reveal geography- and disease-associated herpesvirus antibody repertoires incompletely captured by single-antigen serology.
Authors
- Corinna Bang (ORCID: https://orcid.org/0000-0001-6814-6151)
- Lovro Trgovec-Greif (ORCID: https://orcid.org/0000-0001-7795-0598)
- Aya K.H. Mahdy (ORCID: https://orcid.org/0009-0009-6115-4429)
- Rivo Andry Rakotoarivelo (ORCID: https://orcid.org/0000-0003-3438-8624)
- Ravo Razafindrakoto (ORCID: https://orcid.org/0009-0004-1355-5889)
- Njary Randriamampionona
- Daniela Fusco (ORCID: https://orcid.org/0000-0001-8833-239X)
- Melanie Prinzensteiner (ORCID: https://orcid.org/0009-0002-8208-1141)
- Raphaël Rakotozandrindrainy (ORCID: https://orcid.org/0000-0001-8100-8626)
- Gabriele Mayr B (ORCID: https://orcid.org/0000-0003-2468-5350)
- Hesham ElAbd (ORCID: https://orcid.org/0000-0003-1844-8279)
- Nicolai V Hörstke (ORCID: https://orcid.org/0009-0003-8245-7740)
- Jana Christina Hey (ORCID: https://orcid.org/0009-0008-1848-0096)
- Andre Franke (ORCID: https://orcid.org/0000-0003-1530-5811)
- Tahinamandranto Rasamoelina (ORCID: https://orcid.org/0000-0002-3223-3277)
- Norbert Georg Schwarz
- Mathilde Poyet (ORCID: https://orcid.org/0000-0001-6905-9017)
- Johanna Saalfrank (ORCID: https://orcid.org/0009-0008-3479-4837)
- Alba Troci
- Thomas Vogl
Institutions
- Lithuanian University of Health Sciences (LT)
- University of Antananarivo (MG)
- Christian-Albrechts-Universität zu Kiel (DE)
- Université de Fianarantsoa (MG)
- University Hospital Schleswig-Holstein (DE)
- German Center for Infection Research (DE)
- Medical University of Vienna (AT)
- Bernhard Nocht Institute for Tropical Medicine (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2026-10-27
- DOI
- https://doi.org/10.1016/j.celrep.2026.118200
- Primary Topic
- Viral-associated cancers and disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Deutsche Forschungsgemeinschaft