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125 Naturally C-Terminally Truncated STAT5 (STAT5Δ): A Negative Controller of HIV-1 Transcription and Expression

Chiara, Giulia Della1; Crotti, Andrea1; Giacca, Mauro2; Lusic, Marina2; Poli, Guido1

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 50
doi: 10.1097/01.qai.0000397313.24836.e0

1AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, Milano, ITALY, Department of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milano 20132, Italy; 2Molecular Medicine Laboratory ICGEB Trieste, Padriciano (Trieste) 34012, Italy

Signal transducers and activator of transcription (STAT) proteins, namely STAT1 and STAT5, are often constitutively activated in the PBMC of most of HIV-1+ individuals; furthermore, most patients are characterized by the dominant expression of a C-terminally truncated isoform of STAT5 (STAT5Δ). STAT5Δ is also the prevalent isoform of STAT5 found in the chronically HIV-1 infected promonocytic cell line U1, characterized by a constitutive state of viral latency and inducibility of virus expression by PMA or several cytokines. GM-CSF-mediated STAT5Δ activation induced a delayed expression of integrated HIV-1 in U1 cells. Selective inhibition of STAT5Δ expression or activation enhanced viral expression in GM-CSF stimulated U1 cells. Moreover, activated STAT5Δ can directly in vivo bind to STAT consensus sequences in the HIV-LTR promoter with an impaired recruitment of RNAPol II in U1 cells stimulated with GM-CSF. STAT5Δ can act as a negative regulator of HIV-1 expression in GM-CSF stimulated U1 cells. We are currently investigating whether the reduced recruitment of RNA Pol II and the consequent decreased viral transcription and delayed kinetics of HIV expression that follow GM-CSF stimulation could be entirely attributed to the negative role of STAT5Δ alone or whether other proteins participate to the negative control of HIV transcription in U1 cells.

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