Upregulation of Glucose Uptake and Hexokinase Activity of Primary Human CD4+T Cells in Response to Infection with HIV-1

作者：Williamson Maia Kavanagh; Coombes Naomi; Juszczak Florian; Athanasopoulos Marios; Khan Mariam B; Eykyn Thomas R; Srenathan Ushani; Taams Leonie S; Zeidler Julianna Dias; Da Poian Andrea T; Huthoff Hendrik^*

来源：Viruses-Basel, 2018, 10(3): 114.

DOI：10.3390/v10030114

• HIV-1
• glycolysis
• GLUT1
• GLUT3
• GLUT4
• GLUT6
• hexokinase
• HK1
• T lymphocytes

Infection of primary CD4+ T cells with HIV-1 coincides with an increase in glycolysis. We investigated the expression of glucose transporters (GLUT) and glycolytic enzymes in human CD4+ T cells in response to infection with HIV-1. We demonstrate the co-expression of GLUT1, GLUT3, GLUT4, and GLUT6 in human CD4+ T cells after activation, and their concerted overexpression in HIV-1 infected cells. The investigation of glycolytic enzymes demonstrated activation-dependent expression of hexokinases HK1 and HK2 in human CD4+ T cells, and a highly significant increase in cellular hexokinase enzyme activity in response to infection with HIV-1. HIV-1 infected CD4+ T cells showed a marked increase in expression of HK1, as well as the functionally related voltage-dependent anion channel (VDAC) protein, but not HK2. The elevation of GLUT, HK1, and VDAC expression in HIV-1 infected cells mirrored replication kinetics and was dependent on virus replication, as evidenced by the use of reverse transcription inhibitors. Finally, we demonstrated that the upregulation of HK1 in HIV-1 infected CD4+ T cells is independent of the viral accessory proteins Vpu, Vif, Nef, and Vpr. Though these data are consistent with HIV-1 dependency on CD4+ T cell glucose metabolism, a cellular response mechanism to infection cannot be ruled out.

• 出版日期2018-3