PMID- 17671191 OWN - NLM STAT- MEDLINE DCOM- 20070911 LR - 20131121 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 67 IP - 15 DP - 2007 Aug 1 TI - Cannabinoid modulation of Kaposi's sarcoma-associated herpesvirus infection and transformation. PG - 7230-7 AB - 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 Delta(9)-tetrahydrocannabinol (Delta(9)-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 Delta(9)-THC. We also found that Delta(9)-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 Delta(9)-THC stimulated expression of the KSHV-encoded viral G protein-coupled receptor and Kaposi's sarcoma cell proliferation. Our results indicate that Delta(9)-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. FAU - Zhang, Xuefeng AU - Zhang X AD - Division of Experimental Medicine and Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA. FAU - Wang, Jian Feng AU - Wang JF FAU - Kunos, George AU - Kunos G FAU - Groopman, Jerome E AU - Groopman JE LA - eng GR - 5R01HL061940/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (DNA, Viral) RN - 0 (G protein-coupled receptor, Human herpesvirus 8) RN - 0 (Immediate-Early Proteins) RN - 0 (Receptors, Chemokine) RN - 0 (Rta protein, Human herpesvirus 8) RN - 0 (Trans-Activators) RN - 0 (Viral Proteins) RN - 16849-44-8 (delta(9-11)-tetrahydrocannabinol) RN - 7J8897W37S (Dronabinol) SB - IM MH - Blotting, Western MH - Cell Adhesion MH - Cell Proliferation/drug effects MH - Cell Transformation, Neoplastic/*drug effects MH - Cells, Cultured MH - DNA, Viral/analysis MH - Dronabinol/*analogs & derivatives/pharmacology MH - Endothelium, Vascular/drug effects/pathology/*virology MH - Herpesvirus 8, Human/drug effects/*physiology MH - Humans MH - Immediate-Early Proteins/metabolism MH - Receptors, Chemokine/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Skin/blood supply MH - Trans-Activators/metabolism MH - Transfection MH - Viral Load MH - Viral Proteins/metabolism MH - Virus Replication/drug effects EDAT- 2007/08/03 09:00 MHDA- 2007/09/12 09:00 CRDT- 2007/08/03 09:00 PHST- 2007/08/03 09:00 [pubmed] PHST- 2007/09/12 09:00 [medline] PHST- 2007/08/03 09:00 [entrez] AID - 67/15/7230 [pii] AID - 10.1158/0008-5472.CAN-07-0960 [doi] PST - ppublish SO - Cancer Res. 2007 Aug 1;67(15):7230-7. doi: 10.1158/0008-5472.CAN-07-0960.