Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4+ T cells in chronic chikungunya disease

Abstract Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes acute febrile illness that can progress into chronic arthritis-like disease (CHIKVD) in humans. CD4+ T cells have important functions in CHIKV infection, yet the CHIKV target proteins for these CD4 + T cells are poorly character...

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Main Authors: Rimjhim Agarwal, Calvin Ha, Fernanda H. Côrtes, Yeji Lee, Amparo Martínez-Pérez, Rosa Isela Gálvez, Izabella N. Castillo, Elizabeth J. Phillips, Simon A. Mallal, Angel Balmaseda, Eva Harris, Claudia M. Romero-Vivas, Lakshmanane Premkumar, Andrew K. Falconar, Alba Grifoni, Alessandro Sette, Daniela Weiskopf
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60862-7
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author Rimjhim Agarwal
Calvin Ha
Fernanda H. Côrtes
Yeji Lee
Amparo Martínez-Pérez
Rosa Isela Gálvez
Izabella N. Castillo
Elizabeth J. Phillips
Simon A. Mallal
Angel Balmaseda
Eva Harris
Claudia M. Romero-Vivas
Lakshmanane Premkumar
Andrew K. Falconar
Alba Grifoni
Alessandro Sette
Daniela Weiskopf
author_facet Rimjhim Agarwal
Calvin Ha
Fernanda H. Côrtes
Yeji Lee
Amparo Martínez-Pérez
Rosa Isela Gálvez
Izabella N. Castillo
Elizabeth J. Phillips
Simon A. Mallal
Angel Balmaseda
Eva Harris
Claudia M. Romero-Vivas
Lakshmanane Premkumar
Andrew K. Falconar
Alba Grifoni
Alessandro Sette
Daniela Weiskopf
author_sort Rimjhim Agarwal
collection DOAJ
description Abstract Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes acute febrile illness that can progress into chronic arthritis-like disease (CHIKVD) in humans. CD4+ T cells have important functions in CHIKV infection, yet the CHIKV target proteins for these CD4 + T cells are poorly characterized. Here, by stimulating PBMCs collected from individuals with chronic CHIKVD with peptides spanning the entire CHIKV proteome, we provide a comprehensive landscape of CHIKV CD4+ T cell epitopes. We identify three immunodominant regions and associated core motifs in CHIKV E1, nsP1 and CP proteins. In addition, by in silico assessment of the sequence conservation of CHIKV proteome with closely related alphaviruses, we define CHIKV epitopes conserved across arthritogenic and encephalitic viruses. Overall, our work describes CD4+ T cell targets of CHIKV in humans, thereby assisting in studying the functions of CD4+ T cells in CHIKV pathogenesis and vaccine design.
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spelling doaj-art-582e51b00a8543b6b8a4b4db399f10142025-08-20T03:37:37ZengNature PortfolioNature Communications2041-17232025-07-0116111410.1038/s41467-025-60862-7Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4+ T cells in chronic chikungunya diseaseRimjhim Agarwal0Calvin Ha1Fernanda H. Côrtes2Yeji Lee3Amparo Martínez-Pérez4Rosa Isela Gálvez5Izabella N. Castillo6Elizabeth J. Phillips7Simon A. Mallal8Angel Balmaseda9Eva Harris10Claudia M. Romero-Vivas11Lakshmanane Premkumar12Andrew K. Falconar13Alba Grifoni14Alessandro Sette15Daniela Weiskopf16Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI)Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI)Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI)Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI)Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI)Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI)Department of Microbiology and Immunology, University of North Carolina School of MedicineInstitute for Immunology and Infectious Diseases, Murdoch UniversityInstitute for Immunology and Infectious Diseases, Murdoch UniversitySustainable Sciences InstituteDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, BerkeleyLaboratorio de Enfermedades Tropicales, Departamento de Medicina, Fundación Universidad del NorteDepartment of Microbiology and Immunology, University of North Carolina School of MedicineLaboratorio de Enfermedades Tropicales, Departamento de Medicina, Fundación Universidad del NorteCenter for Vaccine Innovation, La Jolla Institute for Immunology (LJI)Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI)Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI)Abstract Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes acute febrile illness that can progress into chronic arthritis-like disease (CHIKVD) in humans. CD4+ T cells have important functions in CHIKV infection, yet the CHIKV target proteins for these CD4 + T cells are poorly characterized. Here, by stimulating PBMCs collected from individuals with chronic CHIKVD with peptides spanning the entire CHIKV proteome, we provide a comprehensive landscape of CHIKV CD4+ T cell epitopes. We identify three immunodominant regions and associated core motifs in CHIKV E1, nsP1 and CP proteins. In addition, by in silico assessment of the sequence conservation of CHIKV proteome with closely related alphaviruses, we define CHIKV epitopes conserved across arthritogenic and encephalitic viruses. Overall, our work describes CD4+ T cell targets of CHIKV in humans, thereby assisting in studying the functions of CD4+ T cells in CHIKV pathogenesis and vaccine design.https://doi.org/10.1038/s41467-025-60862-7
spellingShingle Rimjhim Agarwal
Calvin Ha
Fernanda H. Côrtes
Yeji Lee
Amparo Martínez-Pérez
Rosa Isela Gálvez
Izabella N. Castillo
Elizabeth J. Phillips
Simon A. Mallal
Angel Balmaseda
Eva Harris
Claudia M. Romero-Vivas
Lakshmanane Premkumar
Andrew K. Falconar
Alba Grifoni
Alessandro Sette
Daniela Weiskopf
Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4+ T cells in chronic chikungunya disease
Nature Communications
title Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4+ T cells in chronic chikungunya disease
title_full Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4+ T cells in chronic chikungunya disease
title_fullStr Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4+ T cells in chronic chikungunya disease
title_full_unstemmed Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4+ T cells in chronic chikungunya disease
title_short Identification of immunogenic and cross-reactive chikungunya virus epitopes for CD4+ T cells in chronic chikungunya disease
title_sort identification of immunogenic and cross reactive chikungunya virus epitopes for cd4 t cells in chronic chikungunya disease
url https://doi.org/10.1038/s41467-025-60862-7
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