Abstract

High Glut1 surface expression is associated with increased glycolytic activity in activated CD4+ T cells. 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 demonstrate hyper-responsive PI3K-mTOR signalling. 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.

Link to publisher’s web site

The authors would like to acknowledge The Alfred Hospital and Clinical Research Core Repository and Specimen Collection Service of the University of Washington, USA through the support of an NIH grant [P30 AI027757] for clinical samples. CSP is funded by the Australian Centre for HIV and Hepatitis Virology Research (ACH2) and a 2010 developmental grant (CNIHR) from the University of Washington Center for AIDS Research (CFAR), an NIH funded program under award number AI027757 which is supported by the following NIH Institutes and Centers (NIAID, NCI, NIMH, NIDA, NICHD, NHLBI, NIA). C.S.P is a recipient of the CNIHR and ACH2 grant. SMC is a recipient of a National Health and Medical Research Council of Australia (NHMRC) Principal Research Fellowship.The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute.