TCR repertoire dynamics and their responses underscores dengue severity

Despite recognizing the immune response's role in dengue progression, the intricate dynamics of T cell receptor (TCR) variations across DENV infection severities remain elusive. This study addresses this gap by analyzing in-house generated RNA-seq data from 112 dengue patients with varying disease severities. Our findings reveal that severe dengue patients exhibit pronounced clinical manifestations including leukopenia, thrombocytopenia, and elevated lymphocyte levels, Intriguingly, these patients also showed increased diversity in γ and δ TCR chains, unique TRGV and TRBV segment usage, and extended δ-CDR3 sequences, suggesting specialized inflammatory functions. Furthermore, mutations in the NS5 and 3'UTR regions of the dengue genome correlated with increased TRDV and TRGV chains, indicating a significant role for these mutations in the prevalence of specific TCR chains during severe infections. Overall, the study highlights the complex role of TCR repertoire in dengue pathogenesis, enhancing our understanding of TCR dynamics for future infectious diseases.

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Publication Details

Journal
iScience
Published
2024-09-17
DOI
https://doi.org/10.1016/j.isci.2024.110983
Citations
6
Primary Topic
Mosquito-borne diseases and control
Type
article
Field-Weighted Citation Impact
3.26

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article

TCR repertoire dynamics and their responses underscores dengue severity

Rajesh Pandey, Kriti Khare, Sunita Yadav, Bansidhar Tarai et al.
6 citations
iScience
Mosquito-borne diseases and control
3.26
article

TCR repertoire dynamics and their responses underscores dengue severity

Rajesh Pandey, Kriti Khare, Sunita Yadav, Bansidhar Tarai, Sandeep Budhiraja
article en
6 citations

Abstract

Despite recognizing the immune response's role in dengue progression, the intricate dynamics of T cell receptor (TCR) variations across DENV infection severities remain elusive. This study addresses this gap by analyzing in-house generated RNA-seq data from 112 dengue patients with varying disease severities. Our findings reveal that severe dengue patients exhibit pronounced clinical manifestations including leukopenia, thrombocytopenia, and elevated lymphocyte levels, Intriguingly, these patients also showed increased diversity in γ and δ TCR chains, unique TRGV and TRBV segment usage, and extended δ-CDR3 sequences, suggesting specialized inflammatory functions. Furthermore, mutations in the NS5 and 3'UTR regions of the dengue genome correlated with increased TRDV and TRGV chains, indicating a significant role for these mutations in the prevalence of specific TCR chains during severe infections. Overall, the study highlights the complex role of TCR repertoire in dengue pathogenesis, enhancing our understanding of TCR dynamics for future infectious diseases.

iScienceVol. 27(10)
Institute of Genomics and Integrative Biology (IN), Max Super Speciality Hospital (IN), Max Healthcare (IN), Academy of Scientific and Innovative Research (IN)
Bill and Melinda Gates Foundation, Rockefeller Foundation
Openalex Percentile: Top 8%
Mosquito-borne diseases and control
3.26
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