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

doi:10.1002/1873-3468.12843

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 journal › Article › peer-review

53 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 language	English
Pages (from-to)	3319-3332
Number of pages	14
Journal	FEBS Letters
Volume	591
Issue number	20
DOIs	https://doi.org/10.1002/1873-3468.12843
State	Published - Oct 2017
Externally published	Yes

Keywords

CD4 T cells
Glut1
HIV
PI3K
cancer
immunometabolism
mTOR

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10.1002/1873-3468.12843

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@article{f3860ed75c3c461bbe653f04a172d387,

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

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 {\textquoteleft}virologically suppressed{\textquoteright} cART-treated HIV+ persons.",

keywords = "CD4 T cells, Glut1, HIV, PI3K, cancer, immunometabolism, mTOR",

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

note = "Publisher Copyright: {\textcopyright} 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies",

year = "2017",

month = oct,

doi = "10.1002/1873-3468.12843",

language = "English",

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AU - Palmer, Clovis S.

AU - Duette, Gabriel A.

AU - Wagner, Marc C.E.

AU - Henstridge, Darren C.

AU - Saleh, Suah

AU - Pereira, Candida

AU - Zhou, Jingling

AU - Simar, David

AU - Lewin, Sharon R.

AU - Ostrowski, Matias

AU - McCune, Joseph M.

AU - Crowe, Suzanne M.

PY - 2017/10

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AB - 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.

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KW - Glut1

KW - HIV

KW - PI3K

KW - cancer

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

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Keywords

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