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
Affiliations
Maia Kavanagh Williamson
Department of Infectious Diseases, King’s College London, Guy’s Hospital, London SE1 9RT, UK
Naomi Coombes
Institute of Infection & Global Health, University of Liverpool, 8 W Derby St., Liverpool L7 3EA, UK
Florian Juszczak
Faculty of Medicine and Pharmacy, University of Mons, Place du Parc 20, 7000 Mons, Belgium
Marios Athanasopoulos
Department of Infectious Diseases, King’s College London, Guy’s Hospital, London SE1 9RT, UK
Mariam B. Khan
Department of Infectious Diseases, King’s College London, Guy’s Hospital, London SE1 9RT, UK
Thomas R. Eykyn
Division of Imaging Sciences and Biomedical Engineering, The Rayne Institute, St. Thomas’ Hospital, King’s College London, Westminster Bridge Road, London SE1 7EH, UK
Ushani Srenathan
Centre for Inflammation Biology and Cancer Immunology (CIBCI), School of Immunology & Microbial Sciences, Department of Inflammation Biology, King’s College London, London SE1 1UL, UK
Leonie S. Taams
Centre for Inflammation Biology and Cancer Immunology (CIBCI), School of Immunology & Microbial Sciences, Department of Inflammation Biology, King’s College London, London SE1 1UL, UK
Julianna Dias Zeidler
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
Andrea T. Da Poian
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil
Hendrik Huthoff
Department of Infectious Diseases, King’s College London, Guy’s Hospital, London SE1 9RT, UK
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.
