A "BAD" day for HIV?

When the HIV virus infects a cell, usually a CD4 T cell, the reverse transcriptase generates the DNA strand from the RNA, which is then integrated into the host cell's genome. In order for the virus to activate transcription of its genes, it must be able to activate transciption in the chromatin context. Tat, a potent trans-activator was shown to associate with p300 and P/CAF in order to activate transcription (Benkirane, 1998). Tat was also shown to bind to a RNA stem loop structure known as TAR, activating HIV gene transcription (Braddock, 1993). I was wondering if a potential mode of viral therapy could take advantage of a predominance of pro-apoptotic factors over anti-apoptotic factors in inducing the cells to undergo apoptosis.

Genetic engineering can allow us to manufacture a mutant HIV virus. This mutant HIV virus should have Bad and Bax downstream of TAR. It can be generated in caspase 9 knockout cells with the help of a helper virus that allows packaging of the recombinant genome. If introduced into a HIV infected cell, the Tat encoded by HIV within the infected cell can transactivate the expression of Bad and Bax, allowing for the predomination of pro-apoptotic factors and leading to the apoptosis of the infected cell (Gavrilescu and Denkers, 2003). A "Bad" day for HIV indeed.

Citations

1) Benkirane M, Chun RF, Xiao H, Ogryzko VV, Howard BH, Nakatani Y, Jeang KT. Activation of integrated provirus requires histone acetyltransferase. p300 and P/CAF are coactivators for HIV-1 Tat. J Biol Chem. 1998 Sep 18;273(38):24898-905.

2) Braddock M, Powell R, Blanchard AD, Kingsman AJ, Kingsman SM. HIV-1 TAR RNA-binding proteins control TAT activation of translation in Xenopus oocytes. FASEB J. 1993 Jan;7(1):214-22.

3) Gavrilescu LC, Denkers EY. Apoptosis and the balance of homeostatic and pathologic responses to protozoan infection. Infect Immun. 2003 Nov;71(11):6109-15.