cyclin t1-dependent genes in activated cd4+ t and macrophage cell lines appear enriched in hiv-1 co-factors细胞周期蛋白t1-dependent基因活化的cd4 + t细胞和巨噬细胞细胞系丰富出现在hiv - 1辅助因子.pdfVIP

Cyclin T1-Dependent Genes in Activated CD4+ T and Macrophage Cell Lines Appear Enriched in HIV-1 Co- Factors Wendong Yu, Rajesh Ramakrishnan, Yan Wang, Karen Chiang, Tzu-Ling Sung, Andrew P. Rice* Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America Abstract HIV-1 is dependent upon cellular co-factors to mediate its replication cycle in CD4+ T cells and macrophages, the two major cell types infected by the virus in vivo. One critical co-factor is Cyclin T1, a subunit of a general RNA polymerase II elongation factor known as P-TEFb. Cyclin T1 is targeted directly by the viral Tat protein to activate proviral transcription. Cyclin T1 is up-regulated when resting CD4+ T cells are activated and during macrophage differentiation or activation, conditions that are also necessary for high levels of HIV-1 replication. Because Cyclin T1 is a subunit of a transcription factor, the up- regulation of Cyclin T1 in these cells results in the induction of cellular genes, some of which might be HIV-1 co-factors. Using shRNA depletions of Cyclin T1 and transcriptional profiling, we identified 54 cellular mRNAs that appear to be Cyclin T1-dependent for their induction in activated CD4+ T Jurkat T cells and during differentiation and activation of MM6 cells, a human monocytic cell line. The promoters for these Cyclin T1-dependent genes (CTDGs) are over-represented in two transcription factor binding sites, SREBP1 and ARP1. Notably, 10 of these CTDGs have been reported to be involved in HIV-1 replication, a significant over-representation of such genes when compared to randomly generated lists of 54 genes (p value,0.00021). The results of siRNA depletion and dominant-negative protein experiments with two CTDGs identified here, CDK11 and Casein kinase 1 gamma 1,