In vivo administration of recombinant IL-2 to individuals infected by HIV down-modulates the binding and expression of the transcription factors ying-yang-1 and leader binding protein-1/late simian virus 40 factor

Leader binding protein-1 (LBP-1)/late SV40 factor (LSF) and ying yang-1 (YY 1) transcription factors are involved in the regulation of HIV expression. In particular, YY1 and LBP-1 have been shown to cooperate in repressing HIV -l-long terminal repeat reporter gene expression by in vitro cotransfection experiments. However, no information is available on the levels of express ion and activation of these transcription factors in PBMC of HIV-infected i ndividuals. Therefore, we have evaluated the expression and DNA binding act ivity of YY1 and LBP-1 (LSF) in PBMC of HIV-infected individuals before, du ring, and after administration of IL-2 in association with antiretroviral t herapy (ART), a regimen under consideration for broad clinical use in this disease based on its ability to stably raise the absolute number of circula ting CD4(+) T lymphocytes. Both YY1- and LBP-1 (LSF)-DNA binding were profo undly down-modulated during administration of IL-2/ART, and a proteolytic a ctivity probably responsible for the reduced expression of the two cellular transcription factors was found activated in PBMC of individuals receiving the immunotherapeutic regimen. This study is the first evidence of modulat ion of cellular transcription factors following IL-2/ART administration and provides a potential correlate of the transient raises in plasma viremia e arly reported in patients receiving IL-2 in the absence of ART, thus unders coring the importance of always administering this cytokine to HIV-infected individuals together with potent antiretrovirals.