|
|
Blood, 15 June 2007, Vol. 109, No. 12, pp. 5380-5389.
Prepublished online as a Blood First Edition Paper on March 1, 2007; DOI 10.1182/blood-2006-08-042556.
 Previous Article | Next Article 
Submitted August 21, 2006
Accepted February 16, 2007
Naturally occurring C-terminally truncated STAT5 is a negative regulator of human immunodeficiency virus-type 1 expression
Andrea Crotti, Marina Lusic, Rossella Lupo, Patricia M.J. Lievens, Elio Liboi, Giulia Della Chiara, Marco Tinelli, Adriano Lazzarin, Bruce K. Patterson, Mauro Giacca, Chiara Bovolenta, and Guido Poli*
AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, Milano, Italy
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy
MolMed SpA, Milano, Italy
Division of Biochemistry, Department of Morphological and Biomedical Sciences, University of Verona Medical School, Verona, Italy
Division of Infectious and Tropical Diseases, Hospital of Lodi, Lodi, Italy
Division of Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy
Department of Pathology & Medicine, Division of Infectious Diseases & Geographic Medicine, Stanford University School of Medicine, Stanford, CA, United States
Vita-Salute San Raffaele University, School of Medicine, Milano, Italy
* Corresponding author; email: poli.guido{at}hsr.it.
CD4+ cells of most individuals infected with the human immunodeficiency virus type-1 (HIV-1) harbor a C-terminally truncated and constitutively activated form of signal transducer and activator of transcription-5 (STAT5 ). We here report that the chronically HIV infected U1 cell line expresses STAT5 but not full length STAT5. Granulocyte-macrophage colony stimulating factor (GM-CSF) stimulation of U1 cells promoted early activation of STAT5 and of extracellular signal regulated kinases (ERKs) followed by later activation of activator protein 1 (AP-1) and HIV expression. Inhibition of ERK/AP-1 by PD98059 abolished, whereas either tyrphostin AG490 or a STAT5 small interfering RNA (siRNA) enhanced, virion production in GM-CSF stimulated U1 cells. Chromatin immunoprecipitation demonstrated the induction of STAT5 binding to STAT consensus sequences in the HIV-1 promoter together with a decreased recruitment of RNA polymerase II after 1 h of GM-CSF stimulation of U1 cells. Downregulation of STAT5 by siRNA resulted in the upregulation of both HIV-1 gag-pol RNA and p24 Gag antigen expression in CD8-depleted leukocytes of several HIV+ individuals cultivated ex vivo in the presence of interleukin-2 (IL-2) but not of IL-7. Thus, the constitutively activated STAT5 present in leukocytes of most HIV+ individuals acts as a negative regulator of HIV expression.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. E. Hogg, G. C. Bowick, N. K. Herzog, M. W. Cloyd, and J. J. Endsley
Induction of granulysin in CD8+ T cells by IL-21 and IL-15 is suppressed by human immunodeficiency virus-1
J. Leukoc. Biol.,
November 1, 2009;
86(5):
1191 - 1203.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. F. Zheng, G. J. Jones, M. Shi, J. C. D. Wiseman, K. J. Marr, B. M. Berenger, S. M. Huston, M. J. Gill, A. M. Krensky, P. Kubes, et al.
Late Expression of Granulysin by Microbicidal CD4+ T Cells Requires PI3K- and STAT5-Dependent Expression of IL-2R{beta} That Is Defective in HIV-Infected Patients
J. Immunol.,
June 1, 2008;
180(11):
7221 - 7229.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. W. Lee, E. R. Sharp, A. O'Mahony, M. G. Rosenberg, D. M. Israelski, G. P. Nolan, and D. F. Nixon
Single-Cell, Phosphoepitope-Specific Analysis Demonstrates Cell Type- and Pathway-Specific Dysregulation of Jak/STAT and MAPK Signaling Associated with In Vivo Human Immunodeficiency Virus Type 1 Infection
J. Virol.,
April 1, 2008;
82(7):
3702 - 3712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
