Journal article
Metabolically active CD4 T cells expressing Glut1 and OX40 preferentially harbor HIV during in vitro infection
CS Palmer, GA Duette, MCE Wagner, DC Henstridge, S Saleh, C Pereira, J Zhou, D Simar, SR Lewin, M Ostrowski, JM McCune, SM Crowe
FEBS Letters | WILEY | Published : 2017
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 itse..
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Awarded by National Institutes of Health
Funding Acknowledgements
The authors 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). CSP 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. We acknowledge the assistance of Geza Paukovic from the AMREP Flow Cytometry Core Facility for flow cytometry training and technical advice. We also thank Mark A. Febbraio for giving us access to the Seahorse Analyzer. We are grateful to Dr Darren Russell who provided a donation to support this research.