Cyclin T1-dependent genes in activated CD4 T and macrophage cell lines appear enriched in HIV-1 co-factors

PLoS One. 2008 Sep 5;3(9):e3146. doi: 10.1371/journal.pone.0003146.


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, suggest that these genes are involved either directly or indirectly in HIV-1 replication. It is likely that the 54 CTDGs identified here include novel HIV-1 co-factors. The presence of CTDGs in the protein space that was available for HIV-1 to sample during its evolution and acquisition of Tat function may provide an explanation for why CTDGs are enriched in viral co-factors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / virology*
  • Casein Kinase I / metabolism
  • Cyclin T
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / metabolism*
  • Gene Expression Regulation, Viral*
  • Genes, Dominant
  • HIV-1 / metabolism*
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation
  • Macrophages / cytology*
  • Macrophages / virology*
  • Monocytes / cytology
  • T-Lymphocytes / cytology
  • tat Gene Products, Human Immunodeficiency Virus / metabolism


  • CCNT1 protein, human
  • Cyclin T
  • Cyclins
  • tat Gene Products, Human Immunodeficiency Virus
  • Casein Kinase I
  • CDK11a protein, human
  • Cyclin-Dependent Kinases