Abstract

Chikungunya virus (CHIKV) is a mosquito-borne re-emerging viral infection that can cause chronic chikungunya viral arthritic disease (CHIKVD), which is characterized by incapacitating arthralgia and inflammation that can last for months to years following infection. Despite CHIKV outbreaks occurring worldwide and several vaccines currently in development, immune responses to CHIKV in humans remains largely understudied, and targets of T cell response are currently unknown. In this study, we tested peripheral blood mononuclear cells (PBMCs) collected from patients diagnosed with CHIKV infection during the 2014-2015 outbreak in Colombia against pools of overlapping peptides sequentially spanning each CHIKV protein. Using high-resolution flow cytometry, we detected robust CHIKV-specific CD4+, but not CD8+ T cell responses, in these patients. Patients still experiencing disease symptoms six years after infection displayed significantly stronger CHIKV-specific CD4+ T cell responses against nsP1, nsP2 and E2 proteins, compared to patients that resolved the infection. CHIKV-specific CD4+ T cells in symptomatic patients displayed a significantly lower Th1 CD4+ helper T cell responses and were enriched within the Th17 CD4+ helper subset, identifying tumor necrosis factor-alpha (TNF α) as the predominantly produced cytokine. In conclusion, this study comprehensively characterizes the T cell response against CHIKV in humans during the chronic phase and provides insights into the role of T cells and possible treatment of CHIKVD.

Competing Interest Statement

D.W. is a consultant for Moderna. The remaining authors declare no competing interests.

Details

Title
Chikungunya-virus-specific CD4+ T cells are associated with chronic chikungunya viral arthritic disease in humans
Author
Chang, James; Agarwal, Rimjhim; Cortes, Fernanda H; Ha, Calvin; Villalpando, John; Castillo, Izabella; Galvez, Rosa Isela; Grifoni, Alba; Sette, Alessandro; Romero-Vivas, Claudia M; Heise, Mark T; Lakshmanane, Prem; Falconar, Andrew Keith; Weiskopf, Daniela
University/institution
Cold Spring Harbor Laboratory Press
Section
New Results
Publication year
2023
Publication date
Nov 21, 2023
Publisher
Cold Spring Harbor Laboratory Press
ISSN
2692-8205
Source type
Working Paper
Language of publication
English
ProQuest document ID
2894169793
Copyright
© 2023. This article is published under http://creativecommons.org/licenses/by-nd/4.0/ (“the License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.