Identification of key genes associated with T cell exhaustion in HIV infection based on transcriptomic data

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BACKGROUND: Human immunodeficiency virus (HIV) is a lentivirus belonging to the retrovirus subclass. HIV specifically targets and infects human CD4 + T lymphocytes, and T cell exhaustion (TEX) plays an important role in disease progression. However, the specific molecular mechanisms have not been fully elucidated. In this study, we explored the potential mechanisms by analyzing transcriptomic data and TEX-related genes, and screened novel markers closely associated with HIV neutralization and T cell function to assess TEX severity and guide precise immunotherapy. METHODS: Transcriptomic data related to HIV were screened from public databases. Key genes associated with TEX were identified through machine learning, receiver operating characteristic curve analyses, and gene expression analyses, and a molecular regulatory network was constructed. Subsequently, methods such as localization analysis, gene set enrichment analysis, and immune infiltration analysis were employed to explore the underlying mechanisms. Finally, the mRNA expression of diagnostic genes in clinical samples was verified by RT-qPCR. RESULTS: EPSTI1 and MSC were identified as key genes. EPSTI1 was enriched in the Epstein-Barr virus infection pathway, whereas MSC was associated with base excision repair. MSC protein was mainly localized in the nucleus, while the subcellular localization of EPSTI1 remained unclear. Immune infiltration analysis revealed the significant differential infiltration of 12 cell types, among which MSC was associated with three cell types and EPSTI1 was associated with one cell type. RT-qPCR results further suggested that EPSTI1 expression was significantly elevated in HIV-infected individuals, and its upregulation was likely positively correlated with the severity of TEX. No statistically significant difference was observed in MSC expression between the two groups. CONCLUSION: This study indicated that EPSTI1 may serve as a potential functional gene during HIV infection. EPSTI1 may be a promising candidate biomarker for TEX in HIV infection and could act as a tentative therapeutic target for follow-up research.

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