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Published online before print June 12, 2001, 10.1101/gr.GR-1802R
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Vol. 11, Issue 7, 1198-1204, July 2001

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

Jacques Corbeil,1,5,8 Dennis Sheeter,2 Davide Genini,1 Steffney Rought,1,5 Lorenzo Leoni,1 Pinyi Du,1 Mark Ferguson,1 Daniel R. Masys,1 John B. Welsh,2 J. Lynn Fink,6 Roman Sasik,3 David Huang,7 Jorg Drenkow,7 Douglas D. Richman,1,2,4,5 and Thomas Gingeras7

Departments of 1 Medicine, 2 Pathology, and 3 Physics, University of California San Diego, La Jolla, California 92023, USA; 4 San Diego Veterans Administration Medical Center, San Diego 92161, USA; 5 Veterans Medical Research Foundation, San Diego 92161, USA; 6 San Diego Supercomputer Center, La Jolla, California 92093, USA; 7 Affymetrix, Santa Clara, California, USA

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.

8 Corresponding author.

11:1198-1204 ©2001 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/01 $5.00
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