Metabolically active CD4+ T cells expressing Glut1 and OX40 preferentially harbor HIV during in vitro infection

Clovis S. Palmer, Gabriel A. Duette, Marc C.E. Wagner, Darren C. Henstridge, Suah Saleh, Candida Pereira, Jingling Zhou, David Simar, Sharon R. Lewin, Matias Ostrowski, Joseph M. McCune, Suzanne M. Crowe

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

High glucose transporter 1 (Glut1) surface expression is associated with increased glycolytic activity in activated CD4+ T cells. Phosphatidylinositide 3-kinases (PI3K) activation measured by p-Akt and OX40 is elevated in CD4+Glut1+ T cells from HIV+ subjects. TCR engagement of CD4+Glut1+ T cells from HIV+ subjects demonstrates hyperresponsive PI3K-mammalian target of rapamycin signaling. High basal Glut1 and OX40 on CD4+ T cells from combination antiretroviral therapy (cART)-treated HIV+ patients represent a sufficiently metabolically active state permissive for HIV infection in vitro without external stimuli. The majority of CD4+OX40+ T cells express Glut1, thus OX40 rather than Glut1 itself may facilitate HIV infection. Furthermore, infection of CD4+ T cells is limited by p110γ PI3K inhibition. Modulating glucose metabolism may limit cellular activation and prevent residual HIV replication in ‘virologically suppressed’ cART-treated HIV+ persons.

Original languageEnglish
Pages (from-to)3319-3332
Number of pages14
JournalFEBS Letters
Volume591
Issue number20
DOIs
StatePublished - Oct 2017
Externally publishedYes

Keywords

  • CD4 T cells
  • Glut1
  • HIV
  • PI3K
  • cancer
  • immunometabolism
  • mTOR

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