HIV-1 Vpu Antagonizes BST-2 by Interfering Mainly with the Trafficking of Newly Synthesized BST-2 to the Cell Surface

Overview

Journal Traffic

Publisher Wiley

Specialties Biology
Physiology

Date 2011 Sep 10

PMID 21902775

Citations 45

Authors

Mathieu Dube

Catherine Paquay

Bibhuti Bhusan Roy

Mariana G Bego

Johanne Mercier

Eric A Cohen

Affiliations

Soon will be listed here.

Abstract

Bone marrow stromal cell antigen-2 (BST-2) inhibits human immunodeficiency virus type 1 (HIV-1) release by cross-linking nascent virions on infected cell surface. HIV-1 Vpu is thought to antagonize BST-2 by downregulating its surface levels via a mechanism that involves intracellular sequestration and lysosomal degradation. Here, we investigated the functional importance of cell-surface BST-2 downregulation and the BST-2 pools targeted by Vpu using an inducible proviral expression system. Vpu established a surface BST-2 equilibrium at ∼60% of its initial levels within 6 h, a condition that coincided with detection of viral release. Analysis of BST-2 post-endocytic trafficking revealed that the protein is engaged in a late endosomal pathway independent of Vpu. While Vpu moderately enhanced cell-surface BST-2 clearance, it strongly affected the protein resupply to the plasma membrane via newly synthesized proteins. Noticeably, Vpu affected clearance of surface BST-2 more substantially in Jurkat T cells than in HeLa cells, suggesting a cell-dependent impact of Vpu on the pool of surface BST-2. Collectively, our data reveal that Vpu imposes a new BST-2 equilibrium, incompatible with efficient restriction of HIV-1 release, by combining an acceleration of surface BST-2 natural clearance, whose degree might be cell-type dependent, to a severe impairment of the protein resupply to the plasma membrane.

Citing Articles

Interactions between HIV proteins and host restriction factors: implications for potential therapeutic intervention in HIV infection.

Rashid F, Zaongo S, Iqbal H, Harypursat V, Song F, Chen Y Front Immunol. 2024; 15:1390650.

PMID: 39221250 PMC: 11361988. DOI: 10.3389/fimmu.2024.1390650.

ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway.

Judith D, Versapuech M, Bejjani F, Palaric M, Verlhac P, Kuster A Proc Natl Acad Sci U S A. 2023; 120(20):e2217451120.

PMID: 37155854 PMC: 10193943. DOI: 10.1073/pnas.2217451120.

Dual Role of HIV-1 Envelope Signal Peptide in Immune Evasion.

Upadhyay C, Rao P, Feyznezhad R Viruses. 2022; 14(4).

PMID: 35458538 PMC: 9030904. DOI: 10.3390/v14040808.

A combined EM and proteomic analysis places HIV-1 Vpu at the crossroads of retromer and ESCRT complexes: PTPN23 is a Vpu-cofactor.

Stoneham C, Langer S, De Jesus P, Wozniak J, Lapek J, Deerinck T PLoS Pathog. 2021; 17(11):e1009409.

PMID: 34843601 PMC: 8659692. DOI: 10.1371/journal.ppat.1009409.

High-Throughput NanoBiT-Based Screening for Inhibitors of HIV-1 Vpu and Host BST-2 Protein Interaction.

Li B, Dong X, Zhang W, Chen T, Yu B, Zhao W Int J Mol Sci. 2021; 22(17).

PMID: 34502213 PMC: 8431494. DOI: 10.3390/ijms22179308.

References

Masuyama N, Kuronita T, Tanaka R, Muto T, Hirota Y, Takigawa A . HM1.24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin. J Biol Chem. 2009; 284(23):15927-41. PMC: 2708888. DOI: 10.1074/jbc.M109.005124. View

Vigan R, Neil S . Determinants of tetherin antagonism in the transmembrane domain of the human immunodeficiency virus type 1 Vpu protein. J Virol. 2010; 84(24):12958-70. PMC: 3004320. DOI: 10.1128/JVI.01699-10. View

Fujita T, Kimura Y, Miyamoto M, Barsoumian E, Taniguchi T . Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1. Nature. 1989; 337(6204):270-2. DOI: 10.1038/337270a0. View

Alain T, Lun X, Martineau Y, Sean P, Pulendran B, Petroulakis E . Vesicular stomatitis virus oncolysis is potentiated by impairing mTORC1-dependent type I IFN production. Proc Natl Acad Sci U S A. 2010; 107(4):1576-81. PMC: 2824402. DOI: 10.1073/pnas.0912344107. View

Waterman H, Katz M, Rubin C, Shtiegman K, Lavi S, Elson A . A mutant EGF-receptor defective in ubiquitylation and endocytosis unveils a role for Grb2 in negative signaling. EMBO J. 2002; 21(3):303-13. PMC: 125825. DOI: 10.1093/emboj/21.3.303. View

Bucci C, Parton R, Mather I, Stunnenberg H, Simons K, Hoflack B . The small GTPase rab5 functions as a regulatory factor in the early endocytic pathway. Cell. 1992; 70(5):715-28. DOI: 10.1016/0092-8674(92)90306-w. View

Mitchell R, Katsura C, Skasko M, Fitzpatrick K, Lau D, Ruiz A . Vpu antagonizes BST-2-mediated restriction of HIV-1 release via beta-TrCP and endo-lysosomal trafficking. PLoS Pathog. 2009; 5(5):e1000450. PMC: 2679223. DOI: 10.1371/journal.ppat.1000450. View

Hammonds J, Wang J, Yi H, Spearman P . Immunoelectron microscopic evidence for Tetherin/BST2 as the physical bridge between HIV-1 virions and the plasma membrane. PLoS Pathog. 2010; 6(2):e1000749. PMC: 2816691. DOI: 10.1371/journal.ppat.1000749. View

Swiecki M, Scheaffer S, Allaire M, Fremont D, Colonna M, Brett T . Structural and biophysical analysis of BST-2/tetherin ectodomains reveals an evolutionary conserved design to inhibit virus release. J Biol Chem. 2010; 286(4):2987-97. PMC: 3024793. DOI: 10.1074/jbc.M110.190538. View

10.

Van Damme N, Goff D, Katsura C, Jorgenson R, Mitchell R, Johnson M . The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe. 2008; 3(4):245-52. PMC: 2474773. DOI: 10.1016/j.chom.2008.03.001. View

11.

Andrew A, Miyagi E, Strebel K . Differential effects of human immunodeficiency virus type 1 Vpu on the stability of BST-2/tetherin. J Virol. 2010; 85(6):2611-9. PMC: 3067951. DOI: 10.1128/JVI.02080-10. View

12.

Kupzig S, Korolchuk V, Rollason R, Sugden A, Wilde A, Banting G . Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic. 2003; 4(10):694-709. DOI: 10.1034/j.1600-0854.2003.00129.x. View

13.

Tervo H, Homann S, Ambiel I, Fritz J, Fackler O, Keppler O . β-TrCP is dispensable for Vpu's ability to overcome the CD317/Tetherin-imposed restriction to HIV-1 release. Retrovirology. 2011; 8:9. PMC: 3049139. DOI: 10.1186/1742-4690-8-9. View

14.

Dube M, Bego M, Paquay C, Cohen E . Modulation of HIV-1-host interaction: role of the Vpu accessory protein. Retrovirology. 2010; 7:114. PMC: 3022690. DOI: 10.1186/1742-4690-7-114. View

15.

Hinz A, Miguet N, Natrajan G, Usami Y, Yamanaka H, Renesto P . Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain. Cell Host Microbe. 2010; 7(4):314-323. PMC: 2859121. DOI: 10.1016/j.chom.2010.03.005. View

16.

Malim M, Emerman M . HIV-1 accessory proteins--ensuring viral survival in a hostile environment. Cell Host Microbe. 2008; 3(6):388-98. DOI: 10.1016/j.chom.2008.04.008. View

17.

Waheed A, Ablan S, Soheilian F, Nagashima K, Ono A, Schaffner C . Inhibition of human immunodeficiency virus type 1 assembly and release by the cholesterol-binding compound amphotericin B methyl ester: evidence for Vpu dependence. J Virol. 2008; 82(19):9776-81. PMC: 2546975. DOI: 10.1128/JVI.00917-08. View

18.

Rong L, Zhang J, Lu J, Pan Q, Lorgeoux R, Aloysius C . The transmembrane domain of BST-2 determines its sensitivity to down-modulation by human immunodeficiency virus type 1 Vpu. J Virol. 2009; 83(15):7536-46. PMC: 2708638. DOI: 10.1128/JVI.00620-09. View

19.

Magadan J, Perez-Victoria F, Sougrat R, Ye Y, Strebel K, Bonifacino J . Multilayered mechanism of CD4 downregulation by HIV-1 Vpu involving distinct ER retention and ERAD targeting steps. PLoS Pathog. 2010; 6(4):e1000869. PMC: 2861688. DOI: 10.1371/journal.ppat.1000869. View

20.

Goffinet C, Homann S, Ambiel I, Tibroni N, Rupp D, Keppler O . Antagonism of CD317 restriction of human immunodeficiency virus type 1 (HIV-1) particle release and depletion of CD317 are separable activities of HIV-1 Vpu. J Virol. 2010; 84(8):4089-94. PMC: 2849503. DOI: 10.1128/JVI.01549-09. View