Tetherin-driven Adaptation of Vpu and Nef Function and the Evolution of Pandemic and Nonpandemic HIV-1 Strains

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2009 Nov 18

PMID 19917496

Citations 288

Authors

Daniel Sauter

Michael Schindler

Anke Specht

Wilmina N Landford

Jan Munch

Kyeong-Ae Kim

Jorg Votteler

Ulrich Schubert

Frederic Bibollet-Ruche

Brandon F Keele

Jun Takehisa

Yudelca Ogando

Christina Ochsenbauer

John C Kappes

Ahidjo Ayouba

Martine Peeters

Gerald H Learn

George Shaw

Paul M Sharp

Paul Bieniasz

Beatrice H Hahn

Theodora Hatziioannou

Frank Kirchhoff

Affiliations

Soon will be listed here.

Abstract

Vpu proteins of pandemic HIV-1 M strains degrade the viral receptor CD4 and antagonize human tetherin to promote viral release and replication. We show that Vpus from SIVgsn, SIVmus, and SIVmon infecting Cercopithecus primate species also degrade CD4 and antagonize tetherin. In contrast, SIVcpz, the immediate precursor of HIV-1, whose Vpu shares a common ancestry with SIVgsn/mus/mon Vpu, uses Nef rather than Vpu to counteract chimpanzee tetherin. Human tetherin, however, is resistant to Nef and thus poses a significant barrier to zoonotic transmission of SIVcpz to humans. Remarkably, Vpus from nonpandemic HIV-1 O strains are poor tetherin antagonists, whereas those from the rare group N viruses do not degrade CD4. Thus, only HIV-1 M evolved a fully functional Vpu following the three independent cross-species transmissions that resulted in HIV-1 groups M, N, and O. This may explain why group M viruses are almost entirely responsible for the global HIV/AIDS pandemic.

Citing Articles

Lysosomal transmembrane protein 5: Impact on immune cell function and implications for immune-related deficiencies.

Sun P, Liao S, Sang P, Liu M, Yang J Heliyon. 2024; 10(17):e36705.

PMID: 39281638 PMC: 11401081. DOI: 10.1016/j.heliyon.2024.e36705.

Antiviral factors and their counteraction by HIV-1: many uncovered and more to be discovered.

Kmiec D, Kirchhoff F J Mol Cell Biol. 2024; 16(2).

PMID: 38318650 PMC: 11334937. DOI: 10.1093/jmcb/mjae005.

Tetherin Restricts SARS-CoV-2 despite the Presence of Multiple Viral Antagonists.

Hagelauer E, Lotke R, Kmiec D, Hu D, Hohner M, Stopper S Viruses. 2023; 15(12).

PMID: 38140605 PMC: 10747847. DOI: 10.3390/v15122364.

The cyclophilin A-binding loop of the capsid regulates the human TRIM5α sensitivity of nonpandemic HIV-1.

Twizerimana A, Becker D, Zhu S, Luedde T, Gohlke H, Munk C Proc Natl Acad Sci U S A. 2023; 120(48):e2306374120.

PMID: 37983491 PMC: 10691330. DOI: 10.1073/pnas.2306374120.

Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo.

Geretz A, Ehrenberg P, Clifford R, Laliberte A, Prelli Bozzo C, Eiser D Sci Transl Med. 2023; 15(707):eadg0873.

PMID: 37531416 PMC: 11651363. DOI: 10.1126/scitranslmed.adg0873.

References

Paul M, Jabbar M . Phosphorylation of both phosphoacceptor sites in the HIV-1 Vpu cytoplasmic domain is essential for Vpu-mediated ER degradation of CD4. Virology. 1997; 232(1):207-16. DOI: 10.1006/viro.1997.8541. View

Dazza M, Ekwalanga M, Nende M, Shamamba K, Bitshi P, Paraskevis D . Characterization of a novel vpu-harboring simian immunodeficiency virus from a Dent's Mona monkey (Cercopithecus mona denti). J Virol. 2005; 79(13):8560-71. PMC: 1143702. DOI: 10.1128/JVI.79.13.8560-8571.2005. View

Barlow K, Ajao A, Clewley J . Characterization of a novel simian immunodeficiency virus (SIVmonNG1) genome sequence from a mona monkey (Cercopithecus mona). J Virol. 2003; 77(12):6879-88. PMC: 156208. DOI: 10.1128/jvi.77.12.6879-6888.2003. View

Bour S, Schubert U, Strebel K . The human immunodeficiency virus type 1 Vpu protein specifically binds to the cytoplasmic domain of CD4: implications for the mechanism of degradation. J Virol. 1995; 69(3):1510-20. PMC: 188742. DOI: 10.1128/JVI.69.3.1510-1520.1995. View

Margottin F, Bour S, Durand H, Selig L, Benichou S, Richard V . A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. Mol Cell. 1998; 1(4):565-74. DOI: 10.1016/s1097-2765(00)80056-8. View

Schubert U, Strebel K . Differential activities of the human immunodeficiency virus type 1-encoded Vpu protein are regulated by phosphorylation and occur in different cellular compartments. J Virol. 1994; 68(4):2260-71. PMC: 236702. DOI: 10.1128/JVI.68.4.2260-2271.1994. View

Cohen E, Terwilliger E, Sodroski J, Haseltine W . Identification of a protein encoded by the vpu gene of HIV-1. Nature. 1988; 334(6182):532-4. DOI: 10.1038/334532a0. View

Schindler M, Wurfl S, Benaroch P, Greenough T, Daniels R, Easterbrook P . Down-modulation of mature major histocompatibility complex class II and up-regulation of invariant chain cell surface expression are well-conserved functions of human and simian immunodeficiency virus nef alleles. J Virol. 2003; 77(19):10548-56. PMC: 228419. DOI: 10.1128/jvi.77.19.10548-10556.2003. View

Jouvenet N, Neil S, Zhadina M, Zang T, Kratovac Z, Lee Y . Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. J Virol. 2008; 83(4):1837-44. PMC: 2643743. DOI: 10.1128/JVI.02211-08. View

10.

Courgnaud V, Salemi M, Pourrut X, Mpoudi-Ngole E, Abela B, Auzel P . Characterization of a novel simian immunodeficiency virus with a vpu gene from greater spot-nosed monkeys (Cercopithecus nictitans) provides new insights into simian/human immunodeficiency virus phylogeny. J Virol. 2002; 76(16):8298-309. PMC: 155126. DOI: 10.1128/jvi.76.16.8298-8309.2002. View

11.

Zennou V, Bieniasz P . Comparative analysis of the antiretroviral activity of APOBEC3G and APOBEC3F from primates. Virology. 2006; 349(1):31-40. DOI: 10.1016/j.virol.2005.12.035. View

12.

Sakuma T, Noda T, Urata S, Kawaoka Y, Yasuda J . Inhibition of Lassa and Marburg virus production by tetherin. J Virol. 2008; 83(5):2382-5. PMC: 2643706. DOI: 10.1128/JVI.01607-08. View

13.

Huet T, Cheynier R, Meyerhans A, Roelants G, Wain-Hobson S . Genetic organization of a chimpanzee lentivirus related to HIV-1. Nature. 1990; 345(6273):356-9. DOI: 10.1038/345356a0. View

14.

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

15.

Bour S, Strebel K . The human immunodeficiency virus (HIV) type 2 envelope protein is a functional complement to HIV type 1 Vpu that enhances particle release of heterologous retroviruses. J Virol. 1996; 70(12):8285-300. PMC: 190916. DOI: 10.1128/JVI.70.12.8285-8300.1996. View

16.

Bailes E, Gao F, Bibollet-Ruche F, Courgnaud V, Peeters M, Marx P . Hybrid origin of SIV in chimpanzees. Science. 2003; 300(5626):1713. DOI: 10.1126/science.1080657. View

17.

Jia B, Serra-Moreno R, Neidermyer W, Rahmberg A, Mackey J, Fofana I . Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2. PLoS Pathog. 2009; 5(5):e1000429. PMC: 2673686. DOI: 10.1371/journal.ppat.1000429. View

18.

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

19.

Gottlinger H, Dorfman T, Cohen E, Haseltine W . Vpu protein of human immunodeficiency virus type 1 enhances the release of capsids produced by gag gene constructs of widely divergent retroviruses. Proc Natl Acad Sci U S A. 1993; 90(15):7381-5. PMC: 47141. DOI: 10.1073/pnas.90.15.7381. View

20.

McNatt M, Zang T, Hatziioannou T, Bartlett M, Fofana I, Johnson W . Species-specific activity of HIV-1 Vpu and positive selection of tetherin transmembrane domain variants. PLoS Pathog. 2009; 5(2):e1000300. PMC: 2633611. DOI: 10.1371/journal.ppat.1000300. View