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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 Factor¹

Chiara Bovolenta^2,*, Laura Camorali^*, Alessandro L. Lorini^*, Giuliana Vallanti^*, Silvia Ghezzi^*, Giuseppe Tambussi, Adriano Lazzarin and Guido Poli^*

^* AIDS Immunophatogenesis Unit, DIBIT, and Division of Infectious Diseases, Centro San Luigi, San Raffaele Scientific Institute, Milan, Italy

Leader binding protein-1 (LBP-1)/late SV40 factor (LSF) and ying yang-1 (YY1) transcription factors are involved in the regulation of HIV expression. In particular, YY1 and LBP-1 have been shown to cooperate in repressing HIV-1-long terminal repeat reporter gene expression by in vitro cotransfection experiments. However, no information is available on the levels of expression and activation of these transcription factors in PBMC of HIV-infected individuals. Therefore, we have evaluated the expression and DNA binding activity of YY1 and LBP-1 (LSF) in PBMC of HIV-infected individuals before, during, and after administration of IL-2 in association with antiretroviral therapy (ART), a regimen under consideration for broad clinical use in this disease based on its ability to stably raise the absolute number of circulating CD4⁺ T lymphocytes. Both YY1- and LBP-1 (LSF)-DNA binding were profoundly down-modulated during administration of IL-2/ART, and a proteolytic activity 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 modulation of cellular transcription factors following IL-2/ART administration and provides a potential correlate of the transient raises in plasma viremia early reported in patients receiving IL-2 in the absence of ART, thus underscoring the importance of always administering this cytokine to HIV-infected individuals together with potent antiretrovirals.

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