c-Myb influences HIV type 1 gene expression and virus production

c-Myb is expressed in proliferating T cells. Fifteen c-Myb-binding sites ca n be identified in the HIV-1 long terminal repeat (LTR), suggesting that c- Myb may regulate HIV-1 gene expression and virus replication. Increasing th e cellular levels of c-Myb by transient transfection of CEM cells resulted in a 10- to 20-fold activation of HIV-1 LTR-driven gene expression and muta tion of one high-affinity Myb-binding site within the LTR reduced this acti vation by 60 to 70%. Conversely, inhibition of c-Myb expression in MT-2 cel ls by treatment with c-myb antisense oligonucleotides decreased HIV-1 repli cation by 85%, as measured by reverse transcriptase activity and cytopathic effects. The effect of c-myb antisense oligonucleotides on HIV-1 gene expr ession and virus particle production appeared to be independent of cell pro liferation, but dependent on the presence of c-Myb activity mediated throug h the HIV-1 LTR. These data show that c-myb expression affects HIV-1 replic ation in CD4(+) T cells.