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FEBS Lett. 2017 Oct;591(20):3319-3332. doi: 10.1002/1873-3468.12843. Epub 2017 Oct 11.

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

Author information

1
Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
2
Department of Infectious Diseases, Monash University, Melbourne, Australia.
3
Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.
4
CONICET-Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Buenos Aires, Argentina.
5
AIDS Cure Research Collaborative, Pittsburgh, PA, USA.
6
Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
7
Monash Micro Imaging, Monash University, Melbourne, Australia.
8
Inflammation and Infection Research, School of Medical Sciences, University of New South Wales, Sydney, Australia.
9
The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia.
10
Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

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.

KEYWORDS:

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

PMID:
28892135
PMCID:
PMC5658250
DOI:
10.1002/1873-3468.12843
[Indexed for MEDLINE]
Free PMC Article

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