Membrane Anchoring by a C-terminal Tryptophan Enables HIV-1 Vpu to Displace Bone Marrow Stromal Antigen 2 (BST2) from Sites of Viral Assembly.

The Journal of Biological Chemistry
Mary K LewinskiJohn C Guatelli

Abstract

The restriction factor BST2 (tetherin) prevents the release of enveloped viruses from the host cell and is counteracted by HIV-1 Vpu. Vpu and BST2 interact directly via their transmembrane domains. This interaction enables Vpu to induce the surface down-regulation and the degradation of BST2, but neither of these activities fully accounts for the ability of Vpu to enhance virion release. During a study of naturally occurring Vpu proteins, we found that a tryptophan residue near the Vpu C terminus is particularly important for enhancing virion release. Vpu proteins with a W76G polymorphism degraded and down-regulated BST2 from the cell surface, yet they inefficiently stimulated virion release. Here we explore the mechanism of this anomaly. We find that Trp-76 is critical for the ability of Vpu to displace BST2 from sites of viral assembly in the plane of the plasma membrane. This effect does not appear to involve a general reorganization of the membrane microdomains associated with virion assembly, but rather is a specific effect of Vpu on BST2. Using NMR spectroscopy, we find that the cytoplasmic domain of Vpu and Trp-76 specifically interact with lipids. Moreover, paramagnetic relaxation enhancement studies show that Trp-76 in...Continue Reading

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Citations

Apr 5, 2016·Immunity, Inflammation and Disease·Wadie D Mahauad-Fernandez, Chioma M Okeoma
Sep 13, 2015·Biochimica Et Biophysica Acta·Hua ZhangStanley J Opella
Aug 8, 2015·Retrovirology·Colin M ExlinePaula M Cannon
Aug 8, 2015·Viruses·María Eugenia González
Sep 28, 2017·Viruses·Olivier LeymarieClarisse Berlioz-Torrent
May 14, 2016·Journal of Virology·François M PujolOliver T Fackler
Sep 23, 2016·Journal of Virology·Juan F AriasDavid T Evans
Jan 9, 2016·The Journal of Biological Chemistry·Dominique DotsonXinhong Dong

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