Abstract
Marijuana and other drugs have been suggested to act as cofactors for HIV infection. Interestingly, Δ9-THC has been shown to upregulate NFKB, a transcription factor utilized by HIV. Therefore, it was of interest to investigate whether cannabinoids can modulate HIV infection and replication. Initially, we tested for evidence of receptor expression by examining for receptor mRNA in various cell lines used to study HIV infection and replication. Cellular RNA was isolated from SupT, and H9, H9MN, and MT-2 cells and RT-PCR was performed. Results showed that, although all of the cell lines tested were positive for CB2 mRNA, only the MT-2 cells also expressed CB1 mRNA. Since the MT-2 cells expressed both CB1 and CB2 receptor mRNA, we next wanted to determine whether different cannabinoid receptor agonists such as CP-55,940, Δ9-THC, WIN-55,212-2, and WIN-55,212-3 influenced infection of these cells by cell free HIV-1MN. Infectivity assays were performed where MT-2 cells were incubated with drug and cell free virus for 90 min., the free virus washed off, and the cells incubated further, and checked for virus growth by syncytia formation. It was found that the drugs significantly increased syncytia formation when MT-2 cells were cultured in the presence of both drug and cell free HIV-1MN. In conclusion, of the cell lines tested, only the MT-2 cells were positive for both CB1 and CB2 mRNA. In addition, since syncytia formation is an indication of virus infection and cytopathicity it was concluded that cannabi- mimetic drugs may enhance HIV-1 infection of susceptible cells.
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References
Blanchard, D. K., C. Newton, T.W. Klein, W.E. II Stewart and H. In vitro and in vivo suppressive effects of delta 9-tetrahydroeannabinol on interferon production by murine spleen cells. Int. J. Immimopharm. 8:819–824, 1986.
Bour, S., Gelezuinas, R., and Wainberg, M.A. The role of CD4 and its downmodulation in establishment and maintenance of HIV-1 infection. Immunological Reviews. 140:147–71, 1994.
Daaka, Y., Zhu, W., Friedman, H., and Klein, T. Induction of Interleukin-2 receptor α gene by Δ9-Tetrahydrocannabinol is mediated by nuclear factor KB and CB1 cannabinoid receptor. DNA and Cell Biology. 16(3): 301–309, 1997.
Devane W.A., L. Hanus, A. Breuer, R.G. Pertwee, L.A. Stevenson, G. Griffin, D. Gibson, A. Mandelbaum, A. Etinger, and R. Mechoulam. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258: 1946–1949, 1992.
Ehlers S. Mielke ME. Blankenstein T. Hahn H. Kinetic analysis of cytokine gene expression in the livers of naive and immune mice infected with Listeria monocytogenes. The immediate early phase in innate resistance and acquired immunity. J. Immunology. 149(9):3016–22, 1992.
Gerard, C.M., Mollereau, C., Vassert, G., and Parmentier, M. Molecular cloning of a human cannabinoid receptor. Biochem. J. 279:129–134, 1991.
Inoue, M., Djordjijevic, D., Fukuma, T., Reddy, E.R, Yokoyama, M.M., and Sagawa, K. Down-regulation of CD4 molecules by the expression of Nef: a quantitative analysis of CD4 antigens on the cell surface. International Immunology. 5(9): 1067–73.
Kinter, L.A., Poli, G., Fox, L., Hardy, E., and Fauci, A.S. HIV replication in IL-2 stimulated peripheral blood mononuclear cells is driven in an autocrine/paracrine manner by endogeneous cytokines. J. Immunol. 154:2448–2459, 1995.
Klein, T.W., Newton, C., Widen, R., Friedman, H. Delta-9-THC injection induces cytokine-mediated mortality of mice infected with Legionella pneumophila. J. Pharm. Exp. Ther. 267:635–640, 1993.
Klein, T.W., Y. Kawakami, C. Newton, and H. Friedman. Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo. J. Toxicol. Environ. Health. 32:465–477, 1991.
Luo, Y.D., M.K. Patel, M.D. Weiderhold, and D.W. Ou. Effects of cannabinoids and cocaine on the mitogen-in-duced transformations of lymphocytes of human and mouse origins. Int. J. Immunopharm. 14:49–56, 1992.
Matsuda, L.A., Lolait, S.J., Brownstein, M.J., Young, A.C., and Bonner, T.I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 346:561–564, 1990.
Mechoulam, R., S. Ben-Shabat, L. Hanus, M. Ligumsky, N.E. Kaminski, A.R. Schatz, A. Gopher, S. Almog, B.R. Martin, D.R. Compton, R.G. Pertwee, G. Griffin, M. Bayewitch, J. Barg, and Z. Vogel. Identification of an endogeneous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharm. 50:83–90, 1995.
Munro, S., Thomas, K.L., and Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65, 1993.
Nahas, G.G., N. Suciu-Foca, J.P. Armand, and A. Morishima. Inhibition of cellular mediated immunity in marihuana smokers. Science 183:419–420, 1974.
Pross, S. H., T.W. Klein, C.A. Newton, and H. Friedman. Differential effects of marijuana components on proliferation of spleen, lymph node and thymus cells in vitro. Int. J. Immunopharm. 9:363–370, 1987.
Rinaldi-Carmona, M., F. Barth, M. Heaulme, D. Shire, B. Calandra, C. Congy, S. Martinez, J. Maruani, G. Neliat, D. Caput, P. Ferrara, P. Soubrie, J.C. Brelier, and G. Le Fur. SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Letters. 350:240–244, 1994.
Shire, D., Carillon, C., Kaghad, M., Calandra, B., Ranald-Carmona, M., Le Fur, G., Caput, D., and Ferrara, P. An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing. J. Biological Chem. 270: 3726–3731, 1995.
Smith, P.B., D. R. Compton, S.P. Welch, R.K. Razdan, R. Mechoulam, and B.R. Martin. The pharmacological activity of anandamide, a putative endogeneous cannabinoid, in mice. J. Pharm. Exp. Ther. 270:219–227, 1994
Zhu, W., Igarashi, T., Friedman, H., and Klein, T.W. Δ9-Tetrahydrocannabinol (THC) causes the variable expression of IL2 receptor subunits. J. Pharm. Exp. Ther. 274(2): 1001–1001, 1995.
Zhu, W., Newton, C., Daaka, Y., Friedman, H., and Klein, T. 9-Tetrahydrocannabinol enhances the secretion of Interleukin 1 from endotoxin-stimulated macrophages. J. Pharm. Exp. Ther. 270:1334–1339, 1994.
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Noe, S.N., Nyland, S.B., Ugen, K., Friedman, H., Klein, T.W. (1998). Cannabinoid Receptor Agonists Enhance Syncytia Formation in MT-2 Cells Infected with Cell Free HIV-1MN . In: Friedman, H., Madden, J.J., Klein, T.W. (eds) Drugs of Abuse, Immunomodulation, and Aids. Advances in Experimental Medicine and Biology, vol 437. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5347-2_25
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DOI: https://doi.org/10.1007/978-1-4615-5347-2_25
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