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Journal of Neuroimmune Pharmacology

, Volume 9, Issue 3, pp 369–379 | Cite as

Δ9-Tetrahydrocannabinol Treatment During Human Monocyte Differentiation Reduces Macrophage Susceptibility to HIV-1 Infection

  • Julie C. Williams
  • Sofia Appelberg
  • Bruce A. Goldberger
  • Thomas W. Klein
  • John W. Sleasman
  • Maureen M. GoodenowEmail author
ORIGINAL ARTICLE

Abstract

The major psychoactive component of marijuana, Δ9-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.

Keywords

Macrophage THC Cannabinoid receptor HIV Differentiation 

Notes

Acknowledgments

We would like to acknowledge Daniel Rodriguez, Chris Little, and Steve Pomeroy for technical assistance and thank Dr. Mark Wallet for helpful comments and critical review of the manuscript. We would also like to thank the University of Florida Interdisciplinary Center for Biotechnology Research cellomics core facility for providing flow cytometers and genomics core facility for Sanger sequencing and access to the ABI 7500 FAST instrument. This study was supported in part by HHS funding from the National Institute for Drug Abuse [DA031017] and by Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) supported by the National Institutes of Child Health and Development [HD40533 and HD40474]. JCW is supported by the Laura McClamma Fellowship at the University of Florida. SA is supported by the University of Florida Alumni graduate fellowship and the Linton E. Grinter fellowship. Additional support was provided by the Robert A. Good endowed Chair in Immunology (University of South Florida), Stephany W. Holloway University Chair for AIDS Research (University of Florida), Center for Research in Pediatric Immune Deficiency and Inflammation, and University of Florida Health Cancer Center.

Conflict of Interest

The authors declare that we have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Julie C. Williams
    • 1
  • Sofia Appelberg
    • 1
  • Bruce A. Goldberger
    • 1
  • Thomas W. Klein
    • 2
  • John W. Sleasman
    • 3
  • Maureen M. Goodenow
    • 1
    Email author
  1. 1.Department of Pathology, Immunology and Laboratory Medicine, College of MedicineUniversity of FloridaGainesvilleUSA
  2. 2.Department of Molecular MedicineUniversity of South FloridaTampaUSA
  3. 3.Department of Pediatrics, Division of Allergy and Immunology, School of MedicineDuke UniversityDurhamUSA

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