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Naturally C-Terminally truncated STAT5 (STAT5Δ): a novel negative controller of HIV-1 transcription and expression

  • 1,
  • 1,
  • 2,
  • 1 and
  • 2
Retrovirology20096 (Suppl 2) :P27

https://doi.org/10.1186/1742-4690-6-S2-P27

  • Published:

Keywords

  • Consensus Sequence
  • Selective Inhibition
  • Late Activation
  • Dependent Pathway
  • Negative Role

We have previously observed that 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) [1]. 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. We recently reported that activated STAT5Δ can act as a negative regulator of HIV-1 expression in GM-CSF stimulated U1 cells and IL-2-stimulated PBMCs. Indeed, in U1 cells we have shown that activated STAT5Δ can directly in vivo bind to STAT consensus sequences in the HIV-LTR promoter with an impaired recruitment of RNAPol II. GM-CSF also triggered the late activation of an ERK/AP-1 dependent pathway inducing HIV-1 expression in U1 cells. Selective inhibition of this pathway turned off, while inhibitors of STAT5 enhanced viral expression in GM-CSF stimulated U1 cells [2]. 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.

Authors’ Affiliations

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

References

  1. Bovolenta C, Camorali L, Lorini AL, Ghezzi S, Vicenzi E, Lazzarin A, Poli G: Constitutive activation of STATs upon in vivo human immunodeficiency virus infection. Blood. 1999, 94: 4202-4209.PubMedGoogle Scholar
  2. Crotti Andrea, Lusic Marina, Lupo Rossella, Patricia Lievens MJ, Liboi Elio, Della Chiara Giulia, Tinelli Marco, Lazzarin Adriano, Patterson Bruce, Giacca Mauro, Bovolenta Chiara, Poli Guido: Naturally occurring C-terminally truncated STAT5 is a negative regulator of HIV-1 expression. Blood. 2007, 109: 5380-5389. 10.1182/blood-2006-08-042556.View ArticlePubMedGoogle Scholar

Copyright

© Chiara et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.

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