Biswas D K, Tius M A, Zhuo J, Pardee A B
Division of Cell Growth and Regulation, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, U.S.A.
J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Jun 1;12(2):120-7. doi: 10.1097/00042560-199606010-00004.
Canventol (2-isopropyl-4-isopropyldencyclohex-2-ene-l-ol), a blocker of tumor necrosis factor alpha (TNF-alpha) release, inhibits human immunodeficiency virus type (HIV-1) production in chronically and acutely infected cells. This effect of Canventol on virus replication could be correlated with its inhibitory influence on necrosis factor (NF)-kappa B activation and HIV-1 long terminal repeat (LTR)-driven reporter gene expression in Jurkat cells and these could be overcome by the administration of TNF-alpha. Canventol inhibits activation of the promoter by the viral protein Tat through a TAR-independent mechanism. The HIV-1 promoter is synergistically upregulated when both the TAR-independent and the TAR-dependent modes of Tat action are in operation. Tat-induced downstream events, such as the production of cytokines like TNF-alpha and NF-kappa B activation, are central for this upregulation. Inhibitors of the respective modes of action of Tat downregulate HIV-1 LTR activation and virus replication.
坎文托（2-异丙基-4-异丙基环已-2-烯-1-醇）是一种肿瘤坏死因子α（TNF-α）释放阻滞剂，可抑制慢性和急性感染细胞中人类免疫缺陷病毒1型（HIV-1）的产生。坎文托对病毒复制的这种作用可能与其对坏死因子（NF）-κB激活的抑制作用以及对Jurkat细胞中HIV-1长末端重复序列（LTR）驱动的报告基因表达的抑制作用相关，而给予TNF-α可克服这些作用。坎文托通过一种不依赖TAR的机制抑制病毒蛋白Tat对启动子的激活。当Tat作用的不依赖TAR模式和依赖TAR模式同时起作用时，HIV-1启动子会协同上调。Tat诱导下游事件，如TNF-α等细胞因子的产生和NF-κB激活，是这种上调的关键。Tat各自作用模式的抑制剂会下调HIV-1 LTR激活和病毒复制。
