慢性基孔肯雅病中CD4 T细胞免疫原性和交叉反应性基孔肯雅病毒表位的鉴定

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

作者信息

Agarwal Rimjhim, Ha Calvin, Côrtes Fernanda H, Lee Yeji, Martínez-Pérez Amparo, Gálvez Rosa Isela, Castillo Izabella N, Phillips Elizabeth J, Mallal Simon A, Balmaseda Angel, Harris Eva, Romero-Vivas Claudia M, Premkumar Lakshmanane, Falconar Andrew K, Grifoni Alba, Sette Alessandro, Weiskopf Daniela

机构信息

Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA.

Biomedical Sciences Graduate Program, School of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA.

出版信息

Nat Commun. 2025 Jul 1;16(1):5756. doi: 10.1038/s41467-025-60862-7.

DOI:10.1038/s41467-025-60862-7

PMID:40592820

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12218217/

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.

摘要

基孔肯雅病毒（CHIKV）是一种由蚊子传播的甲病毒，可导致急性发热疾病，在人类中可能发展为慢性关节炎样疾病（CHIKVD）。CD4 T细胞在CHIKV感染中具有重要功能，但这些CD4 + T细胞的CHIKV靶蛋白特征尚不明确。在这里，通过用覆盖整个CHIKV蛋白质组的肽刺激从慢性CHIKVD患者收集的外周血单核细胞（PBMC），我们提供了CHIKV CD4 T细胞表位的全面概况。我们在CHIKV E1、nsP1和CP蛋白中鉴定出三个免疫显性区域和相关的核心基序。此外，通过对CHIKV蛋白质组与密切相关的甲病毒的序列保守性进行计算机评估，我们定义了在致关节炎和致脑炎病毒中保守的CHIKV表位。总体而言，我们的工作描述了人类中CHIKV的CD4 T细胞靶标，从而有助于研究CD4 T细胞在CHIKV发病机制和疫苗设计中的功能。