2n29

Structural highlights

Function

VPU_HV1H2 Enhances virion budding by targeting host CD4 and Tetherin/BST2 to proteasome degradation. Degradation of CD4 prevents any unwanted premature interactions between viral Env and its host receptor CD4 in the endoplasmic reticulum. Degradation of antiretroviral protein Tetherin/BST2 is important for virion budding, as BST2 tethers new viral particles to the host cell membrane. Mechanistically, Vpu bridges either CD4 or BST2 to BTRC, a substrate recognition subunit of the Skp1/Cullin/F-box protein E3 ubiquitin ligase, induces their ubiquitination and subsequent proteasomal degradation. The alteration of the E3 ligase specificity by Vpu seems to promote the degradation of host IKBKB, leading to NF-kappa-B down-regulation and subsequent apoptosis. Ion channel activity has also been suggested, however, formation of cation-selective channel has been reconstituted ex-vivo in lipid bilayers. It is thus unsure that this activity plays a role in vivo.[HAMAP-Rule:MF_04082]^{[1] [2] [3] [4] [5] [6]}

See Also

• Vpu protein

References

1. ↑ Akari H, Bour S, Kao S, Adachi A, Strebel K. The human immunodeficiency virus type 1 accessory protein Vpu induces apoptosis by suppressing the nuclear factor kappaB-dependent expression of antiapoptotic factors. J Exp Med. 2001 Nov 5;194(9):1299-311. PMID:11696595 doi:10.1084/jem.194.9.1299
2. ↑ Mangeat B, Gers-Huber G, Lehmann M, Zufferey M, Luban J, Piguet V. HIV-1 Vpu neutralizes the antiviral factor Tetherin/BST-2 by binding it and directing its beta-TrCP2-dependent degradation. PLoS Pathog. 2009 Sep;5(9):e1000574. PMID:19730691 doi:10.1371/journal.ppat.1000574
3. ↑ Iwabu Y, Fujita H, Kinomoto M, Kaneko K, Ishizaka Y, Tanaka Y, Sata T, Tokunaga K. HIV-1 accessory protein Vpu internalizes cell-surface BST-2/tetherin through transmembrane interactions leading to lysosomes. J Biol Chem. 2009 Dec 11;284(50):35060-72. PMID:19837671 doi:10.1074/jbc.M109.058305
4. ↑ Pham TN, Lukhele S, Hajjar F, Routy JP, Cohen ÉA. HIV Nef and Vpu protect HIV-infected CD4+ T cells from antibody-mediated cell lysis through down-modulation of CD4 and BST2. Retrovirology. 2014 Feb 6;11:15. PMID:24498878 doi:10.1186/1742-4690-11-15
5. ↑ Jia X, Weber E, Tokarev A, Lewinski M, Rizk M, Suarez M, Guatelli J, Xiong Y. Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1. Elife. 2014 Apr 29;3:e02362. doi: 10.7554/eLife.02362. PMID:24843023
6. ↑ Ewart GD, Sutherland T, Gage PW, Cox GB. The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels. J Virol. 1996 Oct;70(10):7108-15. PMID:8794357 doi:10.1128/JVI.70.10.7108-7115.1996