Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS). HIV infection affects the functions and metabolism of T cells, which may determine the fate of patients; however, the specific pathways activated in different T-cell subtypes (CD4⁺ and CD8⁺ T cells) at different stages of infection remain unclear. We obtained transcriptome data of five individuals each with early HIV infection, chronic progressive HIV infection, and no HIV infection. Weighted gene co-expression network analysis was used to evaluate changes in gene expression to determine the antiviral response. An advanced metabolic algorithm was then applied to compare the alterations in metabolic pathways in the two T-cell subtypes at different infection stages. We identified 23 and 20 co-expressed gene modules in CD4⁺ T and CD8⁺ T cells, respectively. CD4⁺ T cells from individuals in the early HIV infection stage were enriched in genes involved in metabolic and infection-related pathways, whereas CD8⁺ T cells were enriched in genes involved in cell cycle and DNA replication. Three key modules were identified in the network common to the two cell types: NLRP1 modules, RIPK1 modules, and RIPK2 modules. The specific role of NLRP1 in the regulation of HIV infection in the human body remains to be determined. Metabolic functional analysis of the two cells showed that the significantly altered metabolic pathways after HIV infection were valine, leucine, and isoleucine degradation; beta-alanine metabolism; and PPAR signaling pathways. In summary, we found the core gene expression modules and different pathways activated in CD4⁺ and CD8⁺ T cells, along with changes in their metabolic pathways during HIV infection progression. These findings can provide an overall resource for establishing biomarkers to facilitate early diagnosis and potential guidance for new targeted therapeutic strategies.

人类免疫缺陷病毒 (HIV) 会导致获得性免疫缺陷综合征 (AIDS)。HIV感染影响T细胞的功能和代谢，可能决定患者的命运；然而，在不同的 T 细胞亚型（CD4 ⁺和 CD8 ⁺T细胞）在不同感染阶段仍不清楚。我们获得了五个早期 HIV 感染者、慢性进行性 HIV 感染者和无 HIV 感染者的转录组数据。加权基因共表达网络分析用于评估基因表达的变化以确定抗病毒反应。然后应用先进的代谢算法来比较两种 T 细胞亚型在不同感染阶段的代谢途径的变化。我们分别在 CD4 ⁺ T 和 CD8 ⁺ T 细胞中鉴定了 23 和 20 个共表达的基因模块。来自早期 HIV 感染阶段个体的CD4 ⁺ T 细胞富含参与代谢和感染相关途径的基因，而 CD8 ⁺T细胞富含参与细胞周期和DNA复制的基因。在两种细胞类型共有的网络中确定了三个关键模块：NLRP1 模块, RIPK1 模块，和 RIPK2模块。NLRP1 在调节人体内 HIV 感染中的具体作用仍有待确定。两种细胞的代谢功能分析表明，HIV感染后显着改变的代谢途径是缬氨酸、亮氨酸和异亮氨酸降解；β-丙氨酸代谢；和 PPAR 信号通路。总之，我们发现了在 CD4 ⁺和 CD8 ⁺ T 细胞中激活的核心基因表达模块和不同途径，以及在 HIV 感染进展过程中其代谢途径的变化。这些发现可以为建立生物标志物提供整体资源，以促进新的靶向治疗策略的早期诊断和潜在指导。