Akusjärvi Sara Svensson, Ambikan Anoop T, Krishnan Shuba, Gupta Soham, Sperk Maike, Végvári Ákos, Mikaeloff Flora, Healy Katie, Vesterbacka Jan, Nowak Piotr, Sönnerborg Anders, Neogi Ujjwal
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, 141 52 Stockholm, Sweden.
Division of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Campus Solna, 171 65 Stockholm, Sweden.
iScience. 2021 Dec 10;25(1):103607. doi: 10.1016/j.isci.2021.103607. eCollection 2022 Jan 21.
Natural control of HIV-1 is a characteristic of <1% of HIV-1-infected individuals, so called elite controllers (EC). In this study, we sought to identify signaling pathways associated with the EC phenotype using integrative proteo-transcriptomic analysis and immunophenotyping. We found HIF signaling and glycolysis as specific traits of the EC phenotype together with dysregulation of HIF target gene transcription. A higher proportion of HIF-1α and HIF-1β in the nuclei of CD4 and CD8 T cells in the male EC were observed, indicating a potential increased activation of the HIF signaling pathway. Furthermore, intracellular glucose levels were elevated in EC even as the surface expression of the metabolite transporters Glut1 and MCT-1 were decreased on lymphocytes indicative of unique metabolic uptake and flux profile. Combined, our data show that glycolytic modulation and altered HIF signaling is a unique feature of the male EC phenotype that may contribute to natural control of HIV-1.
HIV-1的自然控制是不到1%的HIV-1感染者所具有的特征，这些感染者被称为精英控制者（EC）。在本研究中，我们试图通过综合蛋白质组转录组分析和免疫表型分析来确定与EC表型相关的信号通路。我们发现低氧诱导因子（HIF）信号传导和糖酵解是EC表型的特定特征，同时伴有HIF靶基因转录失调。在男性EC的CD4和CD8 T细胞细胞核中观察到较高比例的HIF-1α和HIF-1β，这表明HIF信号通路的潜在激活增加。此外，即使淋巴细胞上代谢物转运蛋白Glut1和MCT-1的表面表达降低，EC中的细胞内葡萄糖水平仍升高，这表明其具有独特的代谢摄取和通量特征。综合来看，我们的数据表明，糖酵解调节和HIF信号改变是男性EC表型的独特特征，可能有助于HIV-1的自然控制。
