Cocaine potentiates HIV-1 replication in human peripheral blood mononuclear cell cocultures. Involvement of transforming growth factor-beta.
Cocaine use is an important high risk behavior in the AIDS epidemic. In this study, we tested the hypothesis that cocaine potentiates the replication of HIV-1 in human PBMC. A coculture system was used in which PBMC from healthy donors were incubated in the absence (control) or presence of cocaine before activation with PHA. Cocultures were then constituted with PBMC infected with a clinical isolate of HIV-1. HIV-1 replication, which was assessed by the measurement of HIV-1 p24 antigen levels in coculture supernatants, was significantly increased in a dose-dependent manner by cocaine with maximal stimulation at a concentration of 10(-9) M (965 +/- 196 vs 303 +/- 80 pg p24 Ag/ml in control cocultures). Antibodies to transforming growth factor-beta (TGF-beta) blocked cocaine-enhanced HIV-1 replication and purified TGF-beta stimulated viral replication in a manner similar to that observed with cocaine. Augmentation of HIV-1 replication by TGF-beta was maximal at a concentration of 0.01 ng/ml; however, viral proliferation appeared to be inhibited by concentrations of TGF-beta of 1 ng/ml or greater. Taken together, these results indicate that cocaine augments the replication of HIV-1 in PHA-activated PBMC via a mechanism that appears to involve TGF-beta.
Peterson
P K
PK
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415.
Gekker
G
G
Chao
C C
CC
Schut
R
R
Molitor
T W
TW
Balfour
H H
HH
D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008213:Lymphocyte Activation; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects*
D016212:Transforming Growth Factor beta; D003042:Cocaine