HIV-1 Nef Promotes Survival of Myeloid Cells by a Stat3-dependent Pathway

Scott D. Briggs, Beata Scholtz, Jean Marc Jacque, Simon Swingler, Mario Stevenson, Thomas E. Smithgall

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Human immunodeficiency virus Nef is a small myristylated protein that plays a critical role in AIDS progression. Nef binds with high affinity to the SH3 domain of the myeloid-restricted tyrosine kinase Hck in vitro, identifying this Src-related kinase as a possible cellular target for Nef in macrophages. Here we show that Nef activates endogenous Hck in the granulocyte-macrophage colony-stimulating factor-dependent myeloid cell line, TF-1. Unexpectedly, Nef induced cytokine-independent TF-1 cell outgrowth and constitutive activation of the Stat3 transcription factor. Induction of survival required the Nef SH3 binding and membrane-targeting motifs and was blocked by dominant-negative Stat3 mutants. Nef also stimulated Stat3 activation in primary human macrophages, providing evidence for Stat3 as a Nef effector in a target cell for human immunodeficiency virus.

Original languageEnglish
Pages (from-to)25605-25611
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number27
DOIs
StatePublished - Jul 6 2001
Externally publishedYes

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Macrophages
Myeloid Cells
Viruses
HIV-1
Chemical activation
Cells
HIV
src Homology Domains
src-Family Kinases
Granulocyte-Macrophage Colony-Stimulating Factor
Protein-Tyrosine Kinases
Acquired Immunodeficiency Syndrome
Transcription Factors
Phosphotransferases
Cytokines
Membranes
Cell Line
Survival
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry

Cite this

Briggs, S. D., Scholtz, B., Jacque, J. M., Swingler, S., Stevenson, M., & Smithgall, T. E. (2001). HIV-1 Nef Promotes Survival of Myeloid Cells by a Stat3-dependent Pathway. Journal of Biological Chemistry, 276(27), 25605-25611. https://doi.org/10.1074/jbc.M103244200

HIV-1 Nef Promotes Survival of Myeloid Cells by a Stat3-dependent Pathway. / Briggs, Scott D.; Scholtz, Beata; Jacque, Jean Marc; Swingler, Simon; Stevenson, Mario; Smithgall, Thomas E.

In: Journal of Biological Chemistry, Vol. 276, No. 27, 06.07.2001, p. 25605-25611.

Research output: Contribution to journalArticle

Briggs, SD, Scholtz, B, Jacque, JM, Swingler, S, Stevenson, M & Smithgall, TE 2001, 'HIV-1 Nef Promotes Survival of Myeloid Cells by a Stat3-dependent Pathway', Journal of Biological Chemistry, vol. 276, no. 27, pp. 25605-25611. https://doi.org/10.1074/jbc.M103244200
Briggs, Scott D. ; Scholtz, Beata ; Jacque, Jean Marc ; Swingler, Simon ; Stevenson, Mario ; Smithgall, Thomas E. / HIV-1 Nef Promotes Survival of Myeloid Cells by a Stat3-dependent Pathway. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 27. pp. 25605-25611.
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