title: Δ(9)-Tetrahydrocannabinol treatment during human monocyte differentiation reduces macrophage susceptibility to HIV-1 infection.
abstract: The major psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), also acts to suppress inflammatory responses. Receptors for THC, CB1, CB2, and GPR55, are differentially expressed on multiple cell types including monocytes and macrophages, which are important modulators of inflammation in vivo and target cells for HIV-1 infection. Use of recreational and medicinal marijuana is increasing, but the consequences of marijuana exposure on HIV-1 infection are unclear. Ex vivo studies were designed to investigate effects on HIV-1 infection in macrophages exposed to THC during or following differentiation. THC treatment of primary human monocytes during differentiation reduced HIV-1 infection of subsequent macrophages by replication competent or single cycle CCR5 using viruses. In contrast, treatment of macrophages with THC immediately prior to or continuously following HIV-1 exposure failed to alter infection. Specific receptor agonists indicated that the THC effect during monocyte differentiation was mediated primarily through CB2. THC reduced the number of p24 positive cells with little to no effect on virus production per infected cell, while quantitation of intracellular viral gag pinpointed the THC effect to an early event in the viral life cycle. Cells treated during differentiation with THC displayed reduced expression of CD14, CD16, and CD163 and donor dependent increases in mRNA expression of selected viral restriction factors, suggesting a fundamental alteration in phenotype. Ultimately, the mechanism of THC suppression of HIV-1 infection was traced to a reduction in cell surface HIV receptor (CD4, CCR5 and CXCR4) expression that diminished entry efficiency.
authors.affiliation: Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, 2033 Mowry Road, Campus Box 103633, Gainesville, FL, 32610-3663, USA.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Williams
authors.forename: Sofia
authors.initials: S
authors.lastname: Appelberg
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Goldberger
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Klein
authors.forename: John W
authors.initials: JW
authors.lastname: Sleasman
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Goodenow
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000378:metabolism / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology
chemical_list: D013759:Dronabinol