Cannabinoid Modulation of Kaposi's Sarcoma–Associated Herpesvirus Infection and Transformation

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Abstract
Kaposi's sarcoma–associated herpesvirus (KSHV; also named human herpesvirus 8) is necessary but not sufficient for the development of Kaposi's sarcoma. A variety of factors may contribute to the pathogenesis of Kaposi's sarcoma in addition to KSHV. Marijuana is a widely used recreational agent, and Δ9-tetrahydrocannabinol (Δ9-THC), the major active component of marijuana, is prescribed for medicinal use. To evaluate how cannabinoids may affect the pathogenesis of Kaposi's sarcoma, we studied primary human dermal microvascular endothelial cells (HMVEC) exposed to KSHV. There was an increased efficiency of KSHV infection in the presence of low doses of Δ9-THC. We also found that Δ9-THC increased the viral load in KSHV-infected HMVEC through activation of the KSHV lytic switch gene, the open reading frame 50. Furthermore, we observed that Δ9-THC stimulated expression of the KSHV-encoded viral G protein–coupled receptor and Kaposi's sarcoma cell proliferation. Our results indicate that Δ9-THC can enhance KSHV infection and replication and foster KSHV-mediated endothelial transformation. Thus, use of cannabinoids may place individuals at greater risk for the development and progression of Kaposi's sarcoma. [Cancer Res 2007;67(15):7230–7]