Increased uptake and accumulation of vitamin C in human immunodeficiency virus 1-infected hematopoietic cell lines.
Vitamin C (ascorbic acid) is required for normal host defense and functions importantly in cellular redox systems. To define the interrelationship between human immunodeficiency virus (HIV) infection and vitamin C flux at the cellular level, we analyzed vitamin C uptake and its effects on virus production and cellular proliferation in HIV-infected and uninfected human lymphoid, myeloid, and mononuclear phagocyte cell lines. Chronic or acute infection of these cell lines by HIV-1 led to increased expression of glucose transporter 1, associated with increased transport and accumulation of vitamin C. Infected cells also showed increased transport of glucose analogs. Exposure to vitamin C had a complex effect on cell proliferation and viral production. Low concentrations of vitamin C increased or decreased cell proliferation depending on the cell line and either had no effect or caused increased viral production. Exposure to high concentrations of vitamin C preferentially decreased the proliferation and survival of the HIV-infected cells and caused decreased viral production. These findings indicate that HIV infection in lymphocytic, monocytic, and myeloid cell lines leads to increased expression of glucose transporter 1 and consequent increased cellular vitamin C uptake. High concentrations of vitamin C were preferentially toxic to HIV-infected host defense cell lines in vitro.
Rivas
C I
CI
Program in Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Vera
J C
JC
Guaiquil
V H
VH
Velásquez
F V
FV
Bórquez-Ojeda
O A
OA
Cárcamo
J G
JG
Concha
I I
II
Golde
D W
DW
D001205:Ascorbic Acid / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D003683:Dehydroascorbic Acid / Q000378:metabolism; D051272:Glucose Transporter Type 1; D015658:HIV Infections / Q000097:blood*; D015497:HIV-1; D018922:HL-60 Cells; D006601:Hexoses / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology*; D009004:Monosaccharide Transport Proteins / Q000097:blood; D010586:Phagocytes / Q000378:metabolism / Q000821:virology*; D014779:Virus Replication
D051272:Glucose Transporter Type 1; D006601:Hexoses; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid