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

PALMER, CLOVIS S.; DUETTE, GABRIEL A.; WAGNER, MARC C. E.; HENSTRIDGE, DARREN C.; SALEH, SUAH; PEREIRA, CANDIDA; ZHOU, JINGLING; SIMAR, DAVID; LEWIN, SHARON R.; OSTROWSKI, MATIAS; MCCUNE, JOSEPH M.; CROWE, SUZANNE M.

FEBS LETTERS

ELSEVIER SCIENCE BV

Año: 2017 vol. 591 p. 3319 - 3332

0014-5793

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.