Xu Jianting, Pan Jiahui, Liu Xin, Zhang Nan, Zhang Xinyue, Wang Guoqing, Zhang Wenyan
Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
College of Basic Medicine, Jilin University, Changchun, China.
Front Genet. 2021 Sep 16;12:756471. doi: 10.3389/fgene.2021.756471. eCollection 2021.
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: modules modules, and 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）可导致获得性免疫缺陷综合征（AIDS）。HIV感染会影响T细胞的功能和代谢，这可能决定患者的命运；然而，在感染的不同阶段，不同T细胞亚型（CD4和CD8 T细胞）中激活的具体途径仍不清楚。我们获取了分别处于HIV早期感染、慢性进行性HIV感染和未感染HIV的五名个体的转录组数据。采用加权基因共表达网络分析来评估基因表达变化以确定抗病毒反应。然后应用先进的代谢算法比较不同感染阶段两种T细胞亚型代谢途径的改变。我们在CD4 T细胞和CD8 T细胞中分别鉴定出23个和20个共表达基因模块。处于HIV感染早期阶段个体的CD4 T细胞富含参与代谢和感染相关途径的基因，而CD8 T细胞则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鉴定出三个关键模块：模块、模块和模块。NLRP1在人体HIV感染调节中的具体作用仍有待确定。对这两种细胞的代谢功能分析表明，HIV感染后显著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；以及PPAR信号通路。总之，我们发现了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HIV感染进展过程中它们代谢途径的变化。这些发现可为建立生物标志物以促进早期诊断提供全面资源，并为新的靶向治疗策略提供潜在指导。
