Temporal Gene Regulation During HIV-1 Infection of Human CD4+ T Cells

  1. Jacques Corbeil1,5,8,
  2. Dennis Sheeter2,
  3. Davide Genini1,
  4. Steffney Rought1,5,
  5. Lorenzo Leoni1,
  6. Pinyi Du1,
  7. Mark Ferguson1,
  8. Daniel R. Masys1,
  9. John B. Welsh2,
  10. J. Lynn Fink6,
  11. Roman Sasik3,
  12. David Huang7,
  13. Jorg Drenkow7,
  14. Douglas D. Richman1,2,4,5, and
  15. Thomas Gingeras7
  1. Departments of 1Medicine, 2Pathology, and 3Physics, University of California San Diego, La Jolla, California 92023, USA; 4San Diego Veterans Administration Medical Center, San Diego 92161, USA; 5Veterans Medical Research Foundation, San Diego 92161, USA; 6San Diego Supercomputer Center, La Jolla, California 92093, USA; 7Affymetrix, Santa Clara, California, USA

Abstract

CD4+ T-cell depletion is a characteristic of human immunodeficiency virus type 1 (HIV-1) infection. In this study, modulation of mRNA expression of 6800 genes was monitored simultaneously at eight time points in a CD4+ T-cell line (CEM-GFP) during HIV infection. The responses to infection included: (1) >30% decrease at 72 h after infection in overall host-cell production of monitored mRNA synthesis, with the replacement of host-cell mRNA by viral mRNA, (2) suppression of the expression of selected mitochondrial and DNA repair gene transcripts, (3) increased expression of the proapoptotic gene and its gene p53-induced product Bax, and (4) activation of caspases 2, 3, and 9. The intense HIV-1 transcription resulted in the repression of much cellular RNA expression and was associated with the induction of apoptosis of infected cells but not bystander cells. This choreographed host gene response indicated that the subversion of the cell transcriptional machinery for the purpose of HIV-1 replication is akin to genotoxic stress and represents a major factor leading to HIV-induced apoptosis.

Footnotes

  • ↵8 Corresponding author.

  • E-MAIL jcorbeil{at}ucsd.edu; FAX (858) 552-7445.

  • Article published on-line before print: Genome Res., 10.1101/gr.180201.

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.180201.

    • Received January 18, 2001.
    • Accepted April 2, 2001.
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  1. Published in Advance June 12, 2001, doi: 10.1101/gr.180201 Genome Res. 11: 1198-1204 Cold Spring Harbor Laboratory Press

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