The cytoplasmic domain of the HIV-1 glycoprotein gp41 induces NF-κB activation through TGF-β-activated kinase 1

Thomas S. Postler, Ronald Charles Desrosiers

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The human and simian immunodeficiency viruses (HIV and SIV) primarily infect lymphocytes, which must be activated for efficient viral replication. We show that the cytoplasmic domain of the transmembrane glycoprotein gp41 (gp41CD) of both HIV-1 and SIV induces activation of NF-κB, a cellular factor important for proviral genome transcription and lymphocyte activation. This NF-κB activating property localized to a region 12-25 (SIV) or 59-70 (HIV-1) residues from the gp41 membrane-spanning domain. An siRNA-based screen of 42 key NF-κB regulators revealed that gp41CD-mediated activation occurs through the canonical NF-κB pathway via TGF-β-activated kinase 1 (TAK1). TAK1 activity was required for gp41CD-mediated NF-κB activation, and HIV-1-derived gp41CD physically interacted with TAK1 through the same region required for NF-κB activation. Importantly, an NF-κB activation-deficient HIV-1 mutant exhibited increased dependence on cellular activation for replication. These findings demonstrate an evolutionarily conserved role for gp41CD in activating NF-κB to promote infection.

Original languageEnglish (US)
Pages (from-to)181-193
Number of pages13
JournalCell Host and Microbe
Volume11
Issue number2
DOIs
StatePublished - Feb 16 2012
Externally publishedYes

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HIV-1
Glycoproteins
Phosphotransferases
HIV
Simian Immunodeficiency Virus
Lymphocyte Activation
Small Interfering RNA
Transcriptional Activation
Genome
Lymphocytes
Membranes
Infection

ASJC Scopus subject areas

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

Cite this

The cytoplasmic domain of the HIV-1 glycoprotein gp41 induces NF-κB activation through TGF-β-activated kinase 1. / Postler, Thomas S.; Desrosiers, Ronald Charles.

In: Cell Host and Microbe, Vol. 11, No. 2, 16.02.2012, p. 181-193.

Research output: Contribution to journalArticle

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