Accolla Roberto S, Mazza Stefania, De Lerma Barbaro Andrea, De Maria Andrea, Tosi Giovanna
Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Varese, Italy.
Eur J Immunol. 2002 Oct;32(10):2783-91. doi: 10.1002/1521-4141(2002010)32:10<2783::AID-IMMU2783>3.0.CO;2-E.
The expression of HLA class II genes is under the control of a transcriptional activator, CIITA, encoded by the AIR-1 locus. Here we show that CIITA inhibits HIV-1 LTR transactivation mediated by Tat. The inhibition occurred when CIITA and Tat were transiently expressed in cells after transfection and, most importantly, when tat cDNA was transfected in cells expressing CIITA in a constitutive fashion and at physiological levels. Furthermore, CIITA inhibited the HIV-1 LTR transactivation mediated by extracellular Tat protein. CIITA inhibition of Tat function could be reversed by overexpression of Cyclin T1, the cellular cofactor used by Tat to facilitate elongation of viral transcripts. CIITA inhibition of Tat function had a dramatic effect on HIV-1 productive infection of human T cells because CIITA(+) T cells supported very poorly, if any, viral replication. These results indicate that sustained expression of CIITA in HIV-1-susceptible targets may down-regulate viral expression both in cells actively replicating the virus and in silently infected cells requiring exogenous Tat to reactivate virus from latency.
HLA II类基因的表达受AIR-1基因座编码的转录激活因子CIITA的调控。在此我们表明，CIITA可抑制由Tat介导的HIV-1长末端重复序列（LTR）的反式激活。当CIITA和Tat在转染后于细胞中瞬时表达时，这种抑制作用就会发生，而且最重要的是，当tat cDNA转染到以生理水平组成型表达CIITA的细胞中时，也会出现这种抑制作用。此外，CIITA可抑制由细胞外Tat蛋白介导的HIV-1 LTR反式激活。Tat发挥功能时用于促进病毒转录本延伸的细胞辅助因子细胞周期蛋白T1（Cyclin T1）的过表达可逆转CIITA对Tat功能的抑制。CIITA对Tat功能的抑制对HIV-1对人T细胞的有效感染产生了显著影响，因为CIITA(+) T细胞即使有病毒复制，水平也非常低。这些结果表明，在HIV-1易感靶细胞中持续表达CIITA可能会下调在积极复制病毒的细胞以及需要外源性Tat从潜伏状态重新激活病毒的沉默感染细胞中的病毒表达。
