Xinjiang Uighur Autonomous Region Center for Disease Control and Prevention, No. 380 Jianquan 1 road, Tianshan District, Urumqi, Xinjiang 830001, China.
School of Public Health, Xinjiang Medical University, No.4 Liyushan Road, Xinshi District, Urumqi, Xinjiang 830000, China.
Life Sci. 2021 Jan 15;265:118857. doi: 10.1016/j.lfs.2020.118857. Epub 2020 Dec 7.
Antiretroviral therapy (ART) controls viral replication but cannot eradicate an infected virus and restore the immune response of patients.
The gene expression profiles of whole blood, PBMCs, CD4+ and CD8+ T cells were obtained from GSE108297. Coexpression analysis was carried out to evaluate differentially expressed genes (DEGs) between strong and weak responder HIV controllers (HICs). Enrichment analysis was used to explore the biological functions of DEGs. The key genes with common DEGs were screened using the Lasso Cox model. Then, the immune scores of HICs and HAART were calculated by ssGSEA. The content of CD4+ and CD8+ T cells, key genes were verified by flow cytometry, RT-PCR and Western blot analysis.
DEGs were clustered into 24 coexpression modules. DEGs related to general immune responses had the highest correlation with strong responding HICs, while DEGs mainly related to the apoptotic process had the highest correlation with weak responder HICs. The hub genes CD8A and CCT2, as well as the key genes TMEM132C and S100A9, were DEGs in HICs and HARRT. The immune score and flow cytometry showed that CD4+ and CD8+ T cells of HICs were lower than those of HARRT in whole blood. Experiments confirmed the expression of key genes in HICs and HARRT.
The key genes identified in this study highlight the strong responder HICs features that to help the immune system control HIV-1 infection. These results will be useful for developing therapeutic targets.
抗逆转录病毒疗法（ART）可控制病毒复制，但无法根除感染病毒并恢复患者的免疫反应。
从 GSE108297 中获得全血、PBMCs、CD4+和 CD8+T 细胞的基因表达谱。进行共表达分析，以评估强应答和弱应答 HIV 控制器（HIC）之间的差异表达基因（DEGs）。富集分析用于探索 DEGs 的生物学功能。使用 Lasso Cox 模型筛选具有共同 DEGs 的关键基因。然后，通过 ssGSEA 计算 HIC 和 HAART 的免疫评分。通过流式细胞术、RT-PCR 和 Western blot 分析验证 CD4+和 CD8+T 细胞的含量和关键基因。
DEGs 聚类为 24 个共表达模块。与强应答 HICs 相关性最高的是与一般免疫反应相关的 DEGs，而与弱应答 HICs 相关性最高的是主要与凋亡过程相关的 DEGs。关键基因 CD8A 和 CCT2 以及关键基因 TMEM132C 和 S100A9 是 HIC 和 HARRT 的 DEGs。免疫评分和流式细胞术显示，HIC 全血中的 CD4+和 CD8+T 细胞低于 HARRT。实验证实了 HIC 和 HARRT 中关键基因的表达。
本研究中鉴定的关键基因突出了强应答 HICs 的特征，有助于免疫系统控制 HIV-1 感染。这些结果将有助于开发治疗靶点。
