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 includ ed: (1) >30% decrease at 72 h after infection in overall host-cell producti on of monitored mRNA synthesis, with the replacement of host-cell mRNA by v iral mRNA, (2) suppression of the expression of selected mitochondrial and DNA repair gene transcripts, (3) increased expression of the proapoptotic g ene 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 mu ch cellular RNA expression and was associated with the induction of apoptos is of infected cells but not bystander cells. This choreographed host gene response indicated that the subversion of the cell transcriptional machiner y for the purpose of HIV-1 replication is akin to genotoxic stress and repr esents a major factor leading to HIV-induced apoptosis.