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

Cell Host & Microbe
Thomas S Postler, Ronald C Desrosiers

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.

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Citations

Oct 19, 2012·Journal of Virology·Thomas S Postler, Ronald C Desrosiers
Dec 12, 2012·Journal of Virology·Andrey TokarevJohn Guatelli
May 28, 2013·Retrovirology·Eveline Santos da SilvaDanielle Perez Bercoff
Jan 8, 2014·Future Virology·Jean K Gustin, Janet L Douglas
Jun 11, 2014·Retrovirology·Ruikang LiuWentao Qiao
Jun 17, 2014·Trends in Microbiology·Philip R Tedbury, Eric O Freed
Oct 1, 2013·Journal of Molecular Biology·Dominik HotterFrank Kirchhoff
Jul 17, 2012·Trends in Pharmacological Sciences·Hiroaki Sakurai
Sep 20, 2015·Current Opinion in Virology·Jun ZhaoPinghui Feng
Oct 20, 2012·The Journal of General Virology·Jonathan D SteckbeckRonald C Montelaro
Nov 20, 2012·Cell Host & Microbe·Rui Pedro GalãoStuart J D Neil
Apr 28, 2017·Journal of Virology·Armando StanoMichael B Zwick
Sep 25, 2015·Journal of Virology·Ferdinand RoeschOlivier Schwartz
Jan 27, 2017·Journal of Virology·Marta Colomer-Lluch, Ruth Serra-Moreno
Feb 20, 2018·Virology Journal·Cyprien BeraudDanielle Perez Bercoff
Jun 5, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yanhua KangLiyun Shi
Dec 14, 2018·Nature Communications·Sean Matthew McCauleyJeremy Luban
Apr 23, 2021·Journal of Virology·Smitha Srinivasachar Badarinarayan, Daniel Sauter

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