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

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

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Abstract

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.

Original languageEnglish
Article number114
JournalViruses
Volume10
Issue number3
DOIs
Publication statusPublished - 7 Mar 2018

Keywords

  • GLUT1
  • GLUT3
  • GLUT4
  • GLUT6
  • Glycolysis
  • HIV-1
  • HK1
  • Hexokinase
  • T lymphocytes
  • Up-Regulation
  • Gene Expression
  • Hexokinase/metabolism
  • HIV-1/immunology
  • Humans
  • Glucose Transport Proteins, Facilitative/genetics
  • HIV Infections/immunology
  • CD4-Positive T-Lymphocytes/immunology
  • Lymphocyte Activation/immunology
  • Biomarkers
  • Glucose/metabolism
  • Enzyme Activation

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    Kavanagh Williamson, M., Coombes, N., Juszczak, F., Athanasopoulos, M., Khan, M. B., Eykyn, T. R., Srenathan, U., Taams, L. S., Dias Zeidler, J., Da Poian, A. T., & Huthoff, H. (2018). Upregulation of Glucose Uptake and Hexokinase Activity of Primary Human CD4+ T Cells in Response to Infection with HIV-1. Viruses, 10(3), [114]. https://doi.org/10.3390/v10030114