Cannabinoids and morphine differentially affect HIV-1 expression in CD4(+) lymphocyte and microglial cell cultures.
The influence of substances of abuse on the progression of HIV-1 infection is controversial, and pharmacologic factors have been postulated as a potential explanation for conflicting data arising from epidemiological studies and animal models. In the present study, cell culture models of HIV-1 infection were used to test this hypothesis. The synthetic cannabinoid WIN 55,212-2 was found to potently inhibit HIV-1 expression in a concentration- and time-dependent manner in CD4(+) lymphocyte and microglial cell cultures. In sharp contrast, morphine either inhibited or stimulated viral expression, depending upon the time of drug exposure, and marked differences were observed between CD4(+) and microglial cells. Also, WIN 55,212-2 inhibited the stimulatory effect of morphine in HIV-1 infected CD4(+) cells. These in vitro findings support the notion that pharmacologic factors need to be considered in epidemiological studies and animal models that pertain to HIV-1 infection.
Peterson
P K
PK
Minneapolis Medical Research Foundation, 914 S. Eighth Street, Minneapolis, MN 55404, USA. peter137@umn.edu
Gekker
G
G
Hu
S
S
Cabral
G
G
Lokensgard
J R
JR
D000704:Analysis of Variance; D048588:Benzoxazines; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D002186:Cannabinoids / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D009020:Morphine / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D048588:Benzoxazines; D002186:Cannabinoids; D016655:HIV Core Protein p24; D009025:Morpholines; D009281:Naphthalenes; D009294:Narcotics; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009020:Morphine