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Morphine promotes the growth of HIV-1 in human peripheral blood mononuclear cell cocultures
P K Peterson1, B M Sharp, G Gekker
1Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415.
Abstract:
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.
Insights
Morphine significantly enhances HIV-1 replication in human immune cells. This opiate receptor-mediated effect suggests morphine acts as a cofactor in HIV-1 pathogenesis, particularly in intravenous drug users.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Morphine is known to alter human T lymphocyte and monocyte function.
- Previous research suggests a potential link between opiate use and HIV-1 progression.
Purpose of the Study:
- To investigate the effect of morphine on the replication of Human Immunodeficiency Virus type 1 (HIV-1) in human immune cells.
- To determine if morphine promotes HIV-1 growth and elucidate the underlying mechanism.
Main Methods:
- A coculture assay was employed using phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMC) from healthy donors and HIV-1-infected PBMC.
- HIV-1 growth was quantified by measuring p24 antigen concentration in coculture supernatants.
- Dose-response, stereospecificity, and receptor antagonism studies were conducted.
Main Results:
- Morphine markedly increased HIV-1AT growth in cocultures, with a three- to fourfold increase observed at 10(-12) M.
- The augmentation of HIV-1 growth by morphine was dependent on interaction with PHA-activated PBMC.
- Morphine's potentiation effect was stereospecific and inhibited by naloxone and beta-funaltrexamine, indicating opiate receptor involvement.
Conclusions:
- Morphine promotes the replication of HIV-1 in human immune cells.
- Opiate receptors mediate the effect of morphine on HIV-1 growth.
- These findings suggest morphine may act as a cofactor in HIV-1 pathogenesis, especially among intravenous drug users.