HIV Nef Enhances Tat-Mediated Viral Transcription through a hnRNP-K-Nucleated Signaling Complex

Dietlinde Wolf, Vanessa Witte, Pat Clark, Katja Blume, Mathias G Lichtenheld, Andreas S. Baur

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Although dispensable in vitro, HIV Nef enables high-level viral replication in infected hosts by an as yet unexplained mechanism. Previously, we proposed that Nef functionally cooperates with the viral transactivator Tat by derepressing the viral promoter via a Nef-associated kinase complex (NAKC). Here, we demonstrate that hnRNP-K, a host factor thought to facilitate crosstalk between kinases and gene expression, interacts with Nef and, as part of NAKC, nucleates Nef-interacting kinases, including Lck, PKCδ, and PI-3 kinase, leading to Lck and Erk1/2 activation. This strongly increased HIV transcription, which depended on Tat and the NF-kB motif in the viral promoter, but not on NF-kB activation. Depletion of hnRNP-K in a Jurkat model of HIV latency increased Erk1/2 activity and greatly augmented HIV reactivating stimuli. We conclude that hnRNP-K coordinates membrane signaling with transcriptional derepression through Erk1/2 and is targeted by HIV to enable Tat-mediated transcription.

Original languageEnglish
Pages (from-to)398-408
Number of pages11
JournalCell Host and Microbe
Volume4
Issue number4
DOIs
StatePublished - Oct 16 2008

Fingerprint

Heterogeneous-Nuclear Ribonucleoprotein K
HIV
Phosphotransferases
NF-kappa B
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Trans-Activators
Phosphatidylinositol 3-Kinases
Gene Expression
Membranes

Keywords

  • MICROBIO
  • SIGNALING

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

HIV Nef Enhances Tat-Mediated Viral Transcription through a hnRNP-K-Nucleated Signaling Complex. / Wolf, Dietlinde; Witte, Vanessa; Clark, Pat; Blume, Katja; Lichtenheld, Mathias G; Baur, Andreas S.

In: Cell Host and Microbe, Vol. 4, No. 4, 16.10.2008, p. 398-408.

Research output: Contribution to journalArticle

Wolf, Dietlinde ; Witte, Vanessa ; Clark, Pat ; Blume, Katja ; Lichtenheld, Mathias G ; Baur, Andreas S. / HIV Nef Enhances Tat-Mediated Viral Transcription through a hnRNP-K-Nucleated Signaling Complex. In: Cell Host and Microbe. 2008 ; Vol. 4, No. 4. pp. 398-408.
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