Margolis D M, Somasundaran M, Green M R
Program in Molecular Medicine, University of Massachusetts Medical Center, Worcester 01605.
J Virol. 1994 Feb;68(2):905-10. doi: 10.1128/JVI.68.2.905-910.1994.
The transcriptional activity of human immunodeficiency virus type 1 (HIV-1) is affected by many cellular factors. Homologies near the HIV-1 initiator region to the DNA-binding sequences of YY1, a multifunctional transcription factor known to regulate diverse viral and cellular promoters, suggested that YY1 might regulate HIV-1. Antibody to YY1 blocked the formation of complexes by HeLa cell nuclear extract and a DNA oligonucleotide encoding the HIV-1 initiator region. HIV-1 long terminal repeat (LTR) expression, as measured the expression of a transfected LTR-CAT reporter gene, was repressed more than 12-fold by the cotransfection of a YY1 expression vector. HIV-1 production by both COS-1 and CEM cells after transfection of an infectious molecular HIV-1 clone was repressed 7- to 20-fold by cotransfection of a YY1 expression vector. HIV-1 production was also decreased threefold in a CD4-positive lymphocyte cell line chronically infected with HIV-1 (8E5) after transfection of YY1. In situ hybridization studies confirmed that YY1 reduced HIV-1 RNA expression. YY1 may play an important role in the regulation of HIV-1 LTR expression in vivo and virus production by infected cells.
人类免疫缺陷病毒1型（HIV-1）的转录活性受多种细胞因子影响。HIV-1起始区域附近与YY1（一种已知可调节多种病毒和细胞启动子的多功能转录因子）的DNA结合序列存在同源性，这表明YY1可能调节HIV-1。针对YY1的抗体可阻断HeLa细胞核提取物与编码HIV-1起始区域的DNA寡核苷酸形成复合物。通过转染的LTR-CAT报告基因的表达来衡量，HIV-1长末端重复序列（LTR）的表达在共转染YY1表达载体后被抑制了12倍以上。在转染感染性分子HIV-1克隆后，COS-1细胞和CEM细胞产生的HIV-1在共转染YY1表达载体后被抑制了7至20倍。在转染YY1后，长期感染HIV-1的CD4阳性淋巴细胞系（8E5）中HIV-1的产生也减少了三倍。原位杂交研究证实YY1降低了HIV-1 RNA的表达。YY1可能在体内调节HIV-1 LTR表达以及受感染细胞产生病毒的过程中发挥重要作用。
