Heterogeneity of Signal Transducer and Activator of Transcription Binding Sites in the Long-Terminal Repeats of Distinct HIV-1 Subtypes



Andrea Crotti*, 1, Giulia D. Chiara1, Silvia Ghezzi2, Rossella Lupo3, Rienk E Jeeninga4, Elio Liboi5, Patricia M.-J Lievens5, Elisa Vicenzi2, Chiara Bovolenta3, Ben Berkhout4, Guido Poli1, 6
1 AIDS Immunopathogenesis, San Raffaele Scientific Institute, Milano, Italy
2 Viral Pathogens and Biosafety Units, San Raffaele Scientific Institute, Milano, Italy
3 MolMed SpA, Milano, Italy
4 Laboratory of Experimental Virology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherland
5 Division of Biochemistry, Department of Morphological and Biomedical Sciences, University of Verona Medical School, Verona, Italy
6 Vita-Salute San Raffaele University, School of Medicine, Milano, Italy


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2007 Bentham Science Publishers Ltd.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the AIDS Immunopathogenesis, San Raffaele Scientific Institute, P2/P3 Laboratories, Via Olgettina n. 58, 20132, Milano, Italy; Tel: +39-02-2643-4914; Fax: +39-02-2643-4905; E-mail: crotti.andrea@hsr.it


Abstract

HIV-1 can be subdivided into distinct subtypes; the consequences of such a genomic variability remain largely speculative. The long terminal repeats (LTR) control HIV transcription and reflect the major differences of distinct viral subtypes. Three regions in the HIV-1 subtype B LTR are close matches to the Signal Transducer and Activator of Transcription (STAT) consensus sequence. Here, we show heterogeneity in these putative STAT binding sites among HIV-1 LTR subtypes A through G. Transfection of constitutively activated STAT5 lead to transcriptional activation of HIV-1 expression in 293T cells transfected with a reporter assay driven by HIV-1 LTR subtype B. Constitutively activated STAT5 transactivated the LTR of various subtypes in U937 cells with different potency. These findings support and expand the potential relevance of STAT5 activation in HIV infection and may bear relevance for a differential regulation of latency and expression of different subtypes of HIV-1.

Keywords: STAT5, HIV, LTR, virus subtype, cytokines, transcription..