Glut1-mediated glucose transport regulates HIV infection.
Cell cycle entry is commonly considered to positively regulate HIV-1 infection of CD4 T cells, raising the question as to how quiescent lymphocytes, representing a large portion of the viral reservoir, are infected in vivo. Factors such as the homeostatic cytokine IL-7 have been shown to render quiescent T cells permissive to HIV-1 infection, presumably by transiently stimulating their entry into the cell cycle. However, we show here that at physiological oxygen (O(2)) levels (2-5% O(2) tension in lymphoid organs), IL-7 stimulation generates an environment permissive to HIV-1 infection, despite a significantly attenuated level of cell cycle entry. We identify the IL-7-induced increase in Glut1 expression, resulting in augmented glucose uptake, as a key factor in rendering these T lymphocytes susceptible to HIV-1 infection. HIV-1 infection of human T cells is abrogated either by impairment of Glut1 signal transduction or by siRNA-mediated Glut1 down-regulation. Consistent with this, we show that the susceptibility of human thymocyte subsets to HIV-1 infection correlates with Glut1 expression; single-round infection is markedly higher in the Glut1-expressing double-positive thymocyte population than in any of the Glut1-negative subsets. Thus, our studies reveal the Glut1-mediated metabolic pathway as a critical regulator of HIV-1 infection in human CD4 T cells and thymocytes.
Institut de Génétique Moléculaire de Montpellier,  Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5535, F-34293 Montpellier Cedex 5,  France.
Séverine
S
Loisel-Meyer
Louise
L
Swainson
Marco
M
Craveiro
Leal
L
Oburoglu
Cédric
C
Mongellaz
Caroline
C
Costa
Marion
M
Martinez
François-Loic
FL
Cosset
Jean-Luc
JL
Battini
Leonard A
LA
Herzenberg
Leonore A
LA
Herzenberg
Kondala R
KR
Atkuri
Marc
M
Sitbon
Sandrina
S
Kinet
Els
E
Verhoeyen
Naomi
N
Taylor
D000328:Adult; D001692:Biological Transport; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D015658:HIV Infections / Q000503:physiopathology*; D006801:Humans; D015398:Signal Transduction
D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; D005947:Glucose