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 journalArticlepeer-review

36 Scopus citations

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

Keywords

  • MICROBIO
  • SIGNALING

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'HIV Nef Enhances Tat-Mediated Viral Transcription through a hnRNP-K-Nucleated Signaling Complex'. Together they form a unique fingerprint.

Cite this