The mechanism by which human immunodeficiency virus type 1 (HIV-1) causes depletion of CD4+ T cells has until now remained largely unexplained. In the July Genome Research, Jacques Corbeil and colleagues from the University of California San Diego, describe the molecular events triggered by invasion of the HIV, creating a detailed account of the cellular injury that follows HIV infection.
Using microarray technology, Corbeil et al. measured the simultaneous mRNA expression, at eight distinct time points, of 6800 genes in a CD4+ T-cell line during the course of HIV infection. They found that responses to infection included a decrease in overall host cell mRNA synthesis, with the replacement of host cell mRNA by viral mRNA, a suppression of mitochondrial and DNA-repair gene transcripts and increased expression of the p53-induced pro-apoptotic gene Bax and its product, with activation of the apoptotic proteases caspases 2, 3 and 9 (Genome Res 2001, 11:1802).
These findings indicate that the subversion of the cell's transcriptional machinery for the purpose of HIV-1 replication is similar to genotoxic stress and represents a major factor leading to HIV-induced apoptosis.
Corbeil J, Sheeter D, Genini D, Rought S, Leoni L, Du P, Ferguson M, Masys DR, Welsh JB, Fink JL, et al.: Temporal gene regulation during HIV-1 infection of human CD4+ T cells. Genome Res 2001, 11:1802.
University of California San Diego