Single-Cell Transcriptomic Atlas Uncovers the Crucial Role of Monocyte-Derived CXCL10 and Identifies Viremia Biomarkers with Viral Genome Evolution during CHIKV Infection
Abstract
Widespread local transmission of Chikungunya virus (CHIKV) in China poses a severe challenge to public health. However, to date, the immunological characteristics of peripheral blood mononuclear cells (PBMCs) in CHIKV-infected individuals have not been characterized in a systematic manner, and specific plasma biomarkers for clinical diagnosis remain lacking. Herein, we applied single-cell RNA sequencing (scRNA-seq) to construct a high-resolution transcriptomic landscape of PBMCs from CHIKV-infected individuals for the first time. In combination with a 120-plex plasma cytokine assay and next-generation sequencing (NGS) of plasma RNA, we multi-dimensionally characterized the immunological features of CHIKV-infected patients and identified potential plasma biomarkers. Our analyses unveiled extensive activation of innate immune pathways marked by significant upregulation of interferon (IFN)-related signaling pathways in CHIKV-infected individuals. Notably, we identified CXCL10, a factor transcriptionally dominated by monocytes and pre-macrophage subsets, as a potential key immune mediator, and found that plasma host mRNAs including TAP1 and CMPK2, etc., could serve as potential auxiliary biomarkers for clinical diagnosis. Phylogenetic analysis demonstrated that the CHIKV strain circulating in Shenzhen belongs to the East/Central/South African (ECSA) genotype and harbors specific mutations of C-T143A, E2-Q282K and E1-R157K. Collectively, this study systematically depicts the peripheral blood immune responses of CHIKV patients from the perspectives of single-cell transcriptome, plasma host transcriptome and cytokines, providing valuable insights into the immunopathogenesis of CHIKV infection, the development of diagnostic biomarkers and the design of targeted therapeutic strategies.
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