Single-cell profiling reveals immunometabolic remodeling with T-cell dysfunction in HIV-1 infected people.

Background: Immunometabolism plays a vital role in the immunopathogenesis of people living with human immunodeficiency virus type 1 (HIV-1) (PLWH). However, the precise relationship between metabolic profiles and T-cell dysfunction in this population remains unclear. This study aimed to investigate the metabolic reprogramming and underlying mechanisms contributing to T-cell dysfunction in PLWH, highlighting potential pathogenic mechanisms during chronic HIV-1 infection. Methods: This study re-analyzed single-cell RNA sequencing data from the Genome Sequence Archive of the Beijing Institute of Genomics Data Center, Chinese Academy of Sciences. The dataset comprised samples from healthy donors (HD), HIV-1-infected treatment-naive patients (TN), and patients undergoing antiviral therapy. Various analytical approaches-including functional analysis, transcription factor analysis, network analysis, and enrichment analysis-were performed to assess T-cell functional and metabolic characteristics, as well as to identify potential targets within metabolic-epigenetic or non-epigenetic regulatory axes involved in T-cell dysfunction. Results: By analyzing the transcriptional profiles, a total of 58,752 CD4 Conclusion: These findings indicate that amino acid- and IDH2-related metabolism may contribute to the dysfunction of both naive and effector subsets by metabolic-epigenetic or non-epigenetic regulatory axes in PLWH.