Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan.
FEBS Lett. 2012 Oct 19;586(20):3562-8. doi: 10.1016/j.febslet.2012.08.010. Epub 2012 Aug 17.
The identification of cellular proteins that interact with the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) provides a basic understanding of HIV-1 gene expression, which is the major determinant regulating virus replication. We show that ZBRK1 negatively regulates the HIV-1 LTR. Ectopic expression of ZBRK1 represses transcriptional activity of the HIV-1 LTR, whereas the depletion of endogenous ZBRK1 leads to activation of the HIV-1 LTR. The repressor activity of ZBRK1 is required for TRIM28 binding. Furthermore, ZBRK1 is bound to the HIV-1 LTR in vivo. These results indicate that ZBRK1 could be involved in a potent intrinsic antiretroviral defense.
鉴定与人类免疫缺陷病毒 1 型（HIV-1）长末端重复序列（LTR）相互作用的细胞蛋白，为了解 HIV-1 基因表达提供了基础，而 HIV-1 基因表达是调节病毒复制的主要决定因素。我们发现 ZBRK1 负调控 HIV-1 LTR。ZBRK1 的异位表达抑制 HIV-1 LTR 的转录活性，而内源性 ZBRK1 的耗竭则导致 HIV-1 LTR 的激活。ZBRK1 的抑制活性是与 TRIM28 结合所必需的。此外，ZBRK1 与 HIV-1 LTR 在体内结合。这些结果表明，ZBRK1 可能参与了强大的固有抗病毒防御。
