Temporal gene regulation during HIV-1 infection of human CD4+ T cells.
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.
Corbeil
J
J
Department of Medicine, University of California San Diego, La Jolla, California 92023, USA. jcorbeil@ucsd.edu
Sheeter
D
D
Genini
D
D
Rought
S
S
Leoni
L
L
Du
P
P
Ferguson
M
M
Masys
D R
DR
Welsh
J B
JB
Fink
J L
JL
Sasik
R
R
Huang
D
D
Drenkow
J
J
Richman
D D
DD
Gingeras
T
T
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology*; D002461:Cell Line, Transformed; D016195:G2 Phase / Q000235:genetics / Q000276:immunology; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D049452:Green Fluorescent Proteins; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D018655:Lymphocyte Count; D008938:Mitosis / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D014771:Virion / Q000378:metabolism
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins