Morphine promotes the growth of HIV-1 in human peripheral blood mononuclear cell cocultures.
Because morphine has been shown to alter the function of human T lymphocytes and monocytes, we postulated that morphine would promote the growth of HIV-1 in these cells. To test this hypothesis, a coculture assay was used consisting of phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMC) from normal donors and PBMC which had been infected with a viral isolate from an asymptomatic patient, HIV-1AT. The growth of HIV-1AT, as reflected by the concentration of p24 antigen in coculture supernatants, was markedly increased in cocultures that contained morphine. A bell-shaped dose-response curve was observed with three- to fourfold increased growth at a morphine concentration of 10(-12) M. Augmentation of HIV-1AT growth by morphine required an interaction with the PHA-activated donor PBMC. Furthermore, potentiation of HIV-1AT growth by morphine was stereospecific and was antagonized by naloxone and beta-funaltrexamine indicating involvement of an opiate receptor mechanism. These findings provide an additional explanation of how opiates could act as a cofactor in the pathogenesis of HIV-1 in intravenous drug users.
Peterson
P K
PK
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415.
Sharp
B M
BM
Gekker
G
G
Portoghese
P S
PS
Sannerud
K
K
Balfour
H H
HH
D002478:Cells, Cultured; D015683:Gene Products, gag / Q000378:metabolism; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology*; D008213:Lymphocyte Activation; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists; D011957:Receptors, Opioid / Q000378:metabolism; D014758:Viral Core Proteins / Q000378:metabolism
D015683:Gene Products, gag; D016655:HIV Core Protein p24; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D014758:Viral Core Proteins; D009270:Naloxone; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine