Gene expression profile of HIV-1 Tat expressing cells: a close interplay between proliferative and differentiation signals

BMC Biochem. 2002 Jun 10;3:14. doi: 10.1186/1471-2091-3-14.

Abstract

Background: Expression profiling holds great promise for rapid host genome functional analysis. It is plausible that host expression profiling in an infection could serve as a universal phenotype in virally infected cells. Here, we describe the effect of one of the most critical viral activators, Tat, in HIV-1 infected and Tat expressing cells. We utilized microarray analysis from uninfected, latently HIV-1 infected cells, as well as cells that express Tat, to decipher some of the cellular changes associated with this viral activator.

Results: Utilizing uninfected, HIV-1 latently infected cells, and Tat expressing cells, we observed that most of the cellular host genes in Tat expressing cells were down-regulated. The down-regulation in Tat expressing cells is most apparent on cellular receptors that have intrinsic receptor tyrosine kinase (RTK) activity and signal transduction members that mediate RTK function, including Ras-Raf-MEK pathway. Co-activators of transcription, such as p300/CBP and SRC-1, which mediate gene expression related to hormone receptor genes, were also found to be down-regulated. Down-regulation of receptors may allow latent HIV-1 infected cells to either hide from the immune system or avoid extracellular differentiation signals. Some of the genes that were up-regulated included co-receptors for HIV-1 entry, translation machinery, and cell cycle regulatory proteins.

Conclusions: We have demonstrated, through a microarray approach, that HIV-1 Tat is able to regulate many cellular genes that are involved in cell signaling, translation and ultimately control the host proliferative and differentiation signals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Cycle / genetics
  • Cell Differentiation / genetics
  • Cell Division / genetics
  • Chromatin / genetics
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation / genetics
  • Gene Products, tat / genetics*
  • HIV-1 / genetics*
  • HeLa Cells / cytology
  • HeLa Cells / metabolism
  • HeLa Cells / virology
  • Humans
  • Protein Biosynthesis / genetics
  • Signal Transduction / genetics*
  • Thymosin / genetics
  • Transcription Factors / genetics
  • Transcription, Genetic / genetics
  • Tumor Cells, Cultured
  • tat Gene Products, Human Immunodeficiency Virus

Substances

  • Chromatin
  • Gene Products, tat
  • Transcription Factors
  • tat Gene Products, Human Immunodeficiency Virus
  • Thymosin