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Virology Journal
Published in: Virology Journal 1/2017

Open Access 01-12-2017 | Research

Evaluation of the contribution of the transmembrane region to the ectodomain conformation of the human immunodeficiency virus (HIV-1) envelope glycoprotein

Authors: Hanh T. Nguyen, Navid Madani, Haitao Ding, Emerald Elder, Amy Princiotto, Christopher Gu, Patrice Darby, James Alin, Alon Herschhorn, John C. Kappes, Youdong Mao, Joseph G. Sodroski

Published in: Virology Journal | Issue 1/2017

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Abstract

Background

The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env), a Type 1 transmembrane protein, assembles into a trimeric spike complex that mediates virus entry into host cells. The high potential energy of the metastable, unliganded Env trimer is maintained by multiple non-covalent contacts among the gp120 exterior and gp41 transmembrane Env subunits. Structural studies suggest that the gp41 transmembrane region forms a left-handed coiled coil that contributes to the Env trimer interprotomer contacts. Here we evaluate the contribution of the gp41 transmembrane region to the folding and stability of Env trimers.

Methods

Multiple polar/charged amino acid residues, which hypothetically disrupt the stop-transfer signal, were introduced in the proposed lipid-interactive face of the transmembrane coiled coil, allowing release of soluble cleavage-negative Envs containing the modified transmembrane region (TMmod). We also examined effects of cleavage, the cytoplasmic tail and a C-terminal fibritin trimerization (FT) motif on oligomerization, antigenicity and functionality of soluble and membrane-bound Envs.

Results

The introduction of polar/charged amino acids into the transmembrane region resulted in the secretion of soluble Envs from the cell. However, these TMmod Envs primarily formed dimers. By contrast, control cleavage-negative sgp140 Envs lacking the transmembrane region formed soluble trimers, dimers and monomers. TMmod and sgp140 trimers were stabilized by the addition of a C-terminal FT sequence, but still exhibited carbohydrate and antigenic signatures of a flexible ectodomain structure. On the other hand, detergent-solubilized cleaved and uncleaved Envs isolated from the membranes of expressing cells exhibited "tighter” ectodomain structures, based on carbohydrate modifications. These trimers were found to be unstable in detergent solutions, but could be stabilized by the addition of a C-terminal FT moiety. The C-terminal FT domain decreased Env cleavage and syncytium-forming ability by approximately three-fold; alteration of the FT trimerization interface restored Env cleavage and syncytium formation to near-wild-type levels.

Conclusion

The modified transmembrane region was not conducive to trimerization of soluble Envs. However, for HIV-1 Env ectodomains that are minimally modified, membrane-anchored Envs exhibit the most native structures and can be stabilized by appropriately positioned FT domains.
Literature
1.
Wyatt R, Sodroski J. The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science. 1998;280:1884–8.PubMedCrossRef
2.
Allan JS, Coligan JE, Barin F, McLane MF, Sodroski JG, Rosen CA, Haseltine WA, Lee TH, Essex M. Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III. Science. 1985;228:1091–4.PubMedCrossRef
3.
Robey WG, Safai B, Oroszlan S, Arthur LO, Gonda MA, Gallo RC, Fischinger PJ. Characterization of envelope and core structural gene products of HTLV-III with sera from AIDS patients. Science. 1985;228:593–5.PubMedCrossRef
4.
Pal R, Hoke GM, Sarngadharan MG. Role of oligosaccharides in the processing and maturation of envelope glycoproteins of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989;86:3384–8.PubMedPubMedCentralCrossRef
5.
Earl PL, Moss B, Doms RW. Folding, interaction with GRP78-BiP, assembly, and transport of the human immunodeficiency virus type 1 envelope protein. J Virol. 1991;65:2047–55.PubMedPubMedCentral
6.
Otteken A, Earl PL, Moss B. Folding, assembly, and intracellular trafficking of the human immunodeficiency virus type 1 envelope glycoprotein analyzed with monoclonal antibodies recognizing maturational intermediates. J Virol. 1996;70:3407–15.PubMedPubMedCentral
7.
Fennie C, Lasky LA. Model for intracellular folding of the human immunodeficiency virus type 1 gp120. J Virol. 1989;63:639–46.PubMedPubMedCentral
8.
Doores KJ, Bonomelli C, Harvey DJ, Vasiljevic S, Dwek RA, Burton DR, Crispin M, Scanlan CN. Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens. Proc Natl Acad Sci U S A. 2010;107:13800–5.PubMedPubMedCentralCrossRef
9.
Go EP, Herschhorn A, Gu C, Castillo-Menendez L, Zhang S, Mao Y, Chen H, Ding H, Wakefield JK, Hua D, et al. Comparative analysis of the glycosylation profiles of membrane-anchored HIV-1 envelope glycoprotein trimers and soluble gp140. J Virol. 2015;89:8245–57.PubMedPubMedCentralCrossRef
10.
Merkle RK, Helland DE, Welles JL, Shilatifard A, Haseltine WA, Cummings RD. gp160 of HIV-I synthesized by persistently infected Molt-3 cells is terminally glycosylated: evidence that cleavage of gp160 occurs subsequent to oligosaccharide processing. Arch Biochem Biophys. 1991;290:248–57.PubMedCrossRef
11.
Brakch N, Dettin M, Scarinci C, Seidah NG, Di Bello C. Structural investigation and kinetic characterization of potential cleavage sites of HIV GP160 by human furin and PC1. Biochem Biophys Res Commun. 1995;213:356–61.PubMedCrossRef
12.
Haim H, Strack B, Kassa A, Madani N, Wang L, Courter JR, Princiotto A, McGee K, Pacheco B, Seaman MS, et al. Contribution of intrinsic reactivity of the HIV-1 envelope glycoproteins to CD4-independent infection and global inhibitor sensitivity. PLoS Pathog. 2011;7:e1002101.PubMedPubMedCentralCrossRef
13.
Munro JB, Gorman J, Ma X, Zhou Z, Arthos J, Burton DR, Koff WC, Courter JR, Smith 3rd AB, Kwong PD, et al. Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science. 2014;346:759–63.PubMedPubMedCentralCrossRef
14.
Herschhorn A, Ma X, Gu C, Ventura JD, Castillo-Menendez L, Melillo B, Terry DS, Smith 3rd AB, Blanchard SC, Munro JB, et al. Release of gp120 restraints leads to an entry-competent intermediate state of the HIV-1 envelope glycoproteins. MBio. 2016;7:e01598–16.PubMedPubMedCentralCrossRef
15.
Dalgleish AG, Beverley PC, Clapham PR, Crawford DH, Greaves MF, Weiss RA. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984;312:763–7.PubMedCrossRef
16.
Klatzmann D, Champagne E, Chamaret S, Gruest J, Guetard D, Hercend T, Gluckman JC, Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984;312:767–8.PubMedCrossRef
17.
Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996;272:1955–8.PubMedCrossRef
18.
Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, et al. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell. 1996;85:1135–48.PubMedCrossRef
19.
Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996;381:661–6.PubMedCrossRef
20.
Doranz BJ, Rucker J, Yi Y, Smyth RJ, Samson M, Peiper SC, Parmentier M, Collman RG, Doms RW. A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell. 1996;85:1149–58.PubMedCrossRef
21.
Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996;381:667–73.PubMedCrossRef
22.
Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996;272:872–7.PubMedCrossRef
23.
Trkola A, Dragic T, Arthos J, Binley JM, Olson WC, Allaway GP, Cheng-Mayer C, Robinson J, Maddon PJ, Moore JP. CD4-dependent, antibody-sensitive interactions between HIV-1 and its co-receptor CCR-5. Nature. 1996;384:184–7.PubMedCrossRef
24.
Wu L, Gerard NP, Wyatt R, Choe H, Parolin C, Ruffing N, Borsetti A, Cardoso AA, Desjardin E, Newman W, et al. CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature. 1996;384:179–83.PubMedCrossRef
25.
Furuta RA, Wild CT, Weng Y, Weiss CD. Capture of an early fusion-active conformation of HIV-1 gp41. Nat Struct Biol. 1998;5:276–9.PubMedCrossRef
26.
He Y, Vassell R, Zaitseva M, Nguyen N, Yang Z, Weng Y, Weiss CD. Peptides trap the human immunodeficiency virus type 1 envelope glycoprotein fusion intermediate at two sites. J Virol. 2003;77:1666–71.PubMedPubMedCentralCrossRef
27.
Koshiba T, Chan DC. The prefusogenic intermediate of HIV-1 gp41 contains exposed C-peptide regions. J Biol Chem. 2003;278:7573–9.PubMedCrossRef
28.
Si Z, Madani N, Cox JM, Chruma JJ, Klein JC, Schon A, Phan N, Wang L, Biorn AC, Cocklin S, et al. Small-molecule inhibitors of HIV-1 entry block receptor-induced conformational changes in the viral envelope glycoproteins. Proc Natl Acad Sci U S A. 2004;101:5036–41.PubMedPubMedCentralCrossRef
29.
Chan DC, Fass D, Berger JM, Kim PS. Core structure of gp41 from the HIV envelope glycoprotein. Cell. 1997;89:263–73.PubMedCrossRef
30.
31.
Weissenhorn W, Dessen A, Harrison SC, Skehel JJ, Wiley DC. Atomic structure of the ectodomain from HIV-1 gp41. Nature. 1997;387:426–30.PubMedCrossRef
32.
Lu M, Blacklow SC, Kim PS. A trimeric structural domain of the HIV-1 transmembrane glycoprotein. Nat Struct Biol. 1995;2:1075–82.PubMedCrossRef
33.
Melikyan GB, Markosyan RM, Hemmati H, Delmedico MK, Lambert DM, Cohen FS. Evidence that the transition of HIV-1 gp41 into a six-helix bundle, not the bundle configuration, induces membrane fusion. J Cell Biol. 2000;151:413–23.PubMedPubMedCentralCrossRef
34.
Staropoli I, Chanel C, Girard M, Altmeyer R. Processing, stability, and receptor binding properties of oligomeric envelope glycoprotein from a primary HIV-1 isolate. J Biol Chem. 2000;275:35137–45.PubMedCrossRef
35.
Yang X, Farzan M, Wyatt R, Sodroski J. Characterization of stable, soluble trimers containing complete ectodomains of human immunodeficiency virus type 1 envelope glycoproteins. J Virol. 2000;74:5716–25.PubMedPubMedCentralCrossRef
36.
Zhang CW, Chishti Y, Hussey RE, Reinherz EL. Expression, purification, and characterization of recombinant HIV gp140. The gp41 ectodomain of HIV or simian immunodeficiency virus is sufficient to maintain the retroviral envelope glycoprotein as a trimer. J Biol Chem. 2001;276:39577–85.PubMedCrossRef
37.
Earl PL, Sugiura W, Montefiori DC, Broder CC, Lee SA, Wild C, Lifson J, Moss B. Immunogenicity and protective efficacy of oligomeric human immunodeficiency virus type 1 gp140. J Virol. 2001;75:645–53.PubMedPubMedCentralCrossRef
38.
Srivastava IK, Stamatatos L, Legg H, Kan E, Fong A, Coates SR, Leung L, Wininger M, Donnelly JJ, Ulmer JB, et al. Purification and characterization of oligomeric envelope glycoprotein from a primary R5 subtype B human immunodeficiency virus. J Virol. 2002;76:2835–47.PubMedPubMedCentralCrossRef
39.
Jeffs SA, Goriup S, Kebble B, Crane D, Bolgiano B, Sattentau Q, Jones S, Holmes H. Expression and characterisation of recombinant oligomeric envelope glycoproteins derived from primary isolates of HIV-1. Vaccine. 2004;22:1032–46.PubMedCrossRef
40.
Qiao ZS, Kim M, Reinhold B, Montefiori D, Wang JH, Reinherz EL. Design, expression, and immunogenicity of a soluble HIV trimeric envelope fragment adopting a prefusion gp41 configuration. J Biol Chem. 2005;280:23138–46.PubMedCrossRef
41.
Pancera M, Lebowitz J, Schon A, Zhu P, Freire E, Kwong PD, Roux KH, Sodroski J, Wyatt R. Soluble mimetics of human immunodeficiency virus type 1 viral spikes produced by replacement of the native trimerization domain with a heterologous trimerization motif: characterization and ligand binding analysis. J Virol. 2005;79:9954–69.PubMedPubMedCentralCrossRef
42.
Li Y, Svehla K, Mathy NL, Voss G, Mascola JR, Wyatt R. Characterization of antibody responses elicited by human immunodeficiency virus type 1 primary isolate trimeric and monomeric envelope glycoproteins in selected adjuvants. J Virol. 2006;80:1414–26.PubMedPubMedCentralCrossRef
43.
Forsell MN, Li Y, Sundback M, Svehla K, Liljestrom P, Mascola JR, Wyatt R, Karlsson Hedestam GB. Biochemical and immunogenic characterization of soluble human immunodeficiency virus type 1 envelope glycoprotein trimers expressed by semliki forest virus. J Virol. 2005;79:10902–14.PubMedPubMedCentralCrossRef
44.
Du SX, Idiart RJ, Mariano EB, Chen H, Jiang P, Xu L, Ostrow KM, Wrin T, Phung P, Binley JM, et al. Effect of trimerization motifs on quaternary structure, antigenicity, and immunogenicity of a non-cleavable HIV-1 gp140 envelope glycoprotein. Virology. 2009;395:33–44.PubMedPubMedCentralCrossRef
45.
Yang X, Lee J, Mahony EM, Kwong PD, Wyatt R, Sodroski J. Highly stable trimers formed by human immunodeficiency virus type 1 envelope glycoproteins fused with the trimeric motif of T4 bacteriophage fibritin. J Virol. 2002;76:4634–42.PubMedPubMedCentralCrossRef
46.
Kovacs JM, Nkolola JP, Peng H, Cheung A, Perry J, Miller CA, Seaman MS, Barouch DH, Chen B. HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120. Proc Natl Acad Sci U S A. 2012;109:12111–6.PubMedPubMedCentralCrossRef
47.
Kovacs JM, Noeldeke E, Ha HJ, Peng H, Rits-Volloch S, Harrison SC, Chen B. Stable, uncleaved HIV-1 envelope glycoprotein gp140 forms a tightly folded trimer with a native-like structure. Proc Natl Acad Sci U S A. 2014;111:18542–7.PubMedPubMedCentralCrossRef
48.
Binley JM, Sanders RW, Clas B, Schuelke N, Master A, Guo Y, Kajumo F, Anselma DJ, Maddon PJ, Olson WC, et al. A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure. J Virol. 2000;74:627–43.PubMedPubMedCentralCrossRef
49.
Sanders RW, Schiffner L, Master A, Kajumo F, Guo Y, Dragic T, Moore JP, Binley JM. Variable-loop-deleted variants of the human immunodeficiency virus type 1 envelope glycoprotein can be stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits. J Virol. 2000;74:5091–100.PubMedPubMedCentralCrossRef
50.
Sanders RW, Vesanen M, Schuelke N, Master A, Schiffner L, Kalyanaraman R, Paluch M, Berkhout B, Maddon PJ, Olson WC, et al. Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J Virol. 2002;76:8875–89.PubMedPubMedCentralCrossRef
51.
Schulke N, Vesanen MS, Sanders RW, Zhu P, Lu M, Anselma DJ, Villa AR, Parren PW, Binley JM, Roux KH, et al. Oligomeric and conformational properties of a proteolytically mature, disulfide-stabilized human immunodeficiency virus type 1 gp140 envelope glycoprotein. J Virol. 2002;76:7760–76.PubMedPubMedCentralCrossRef
52.
Klasse PJ, Depetris RS, Pejchal R, Julien JP, Khayat R, Lee JH, Marozsan AJ, Cupo A, Cocco N, Korzun J, et al. Influences on trimerization and aggregation of soluble, cleaved HIV-1 SOSIP envelope glycoprotein. J Virol. 2013;87:9873–85.PubMedPubMedCentralCrossRef
53.
Khayat R, Lee JH, Julien JP, Cupo A, Klasse PJ, Sanders RW, Moore JP, Wilson IA, Ward AB. Structural characterization of cleaved, soluble HIV-1 envelope glycoprotein trimers. J Virol. 2013;87:9865–72.PubMedPubMedCentralCrossRef
54.
Ringe RP, Sanders RW, Yasmeen A, Kim HJ, Lee JH, Cupo A, Korzun J, Derking R, van Montfort T, Julien JP, et al. Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation. Proc Natl Acad Sci U S A. 2013;110:18256–61.PubMedPubMedCentralCrossRef
55.
Ringe RP, Yasmeen A, Ozorowski G, Go EP, Pritchard LK, Guttman M, Ketas TA, Cottrell CA, Wilson IA, Sanders RW, et al. Influences on the design and purification of soluble, recombinant native-like HIV-1 envelope glycoprotein trimers. J Virol. 2015;89:12189–210.PubMedPubMedCentralCrossRef
56.
Sanders RW, Derking R, Cupo A, Julien JP, Yasmeen A, de Val N, Kim HJ, Blattner C, de la Pena AT, Korzun J, et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog. 2013;9:e1003618.PubMedPubMedCentralCrossRef
57.
Guenaga J, de Val N, Tran K, Feng Y, Satchwell K, Ward AB, Wyatt RT. Well-ordered trimeric HIV-1 subtype B and C soluble spike mimetics generated by negative selection display native-like properties. PLoS Pathog. 2015;11:e1004570.PubMedPubMedCentralCrossRef
58.
Georgiev IS, Joyce MG, Yang Y, Sastry M, Zhang B, Baxa U, Chen RE, Druz A, Lees CR, Narpala S, et al. Single-chain soluble BG505.SOSIP gp140 trimers as structural and antigenic mimics of mature closed HIV-1 Env. J Virol. 2015;89:5318–29.PubMedPubMedCentralCrossRef
59.
Sharma SK, de Val N, Bale S, Guenaga J, Tran K, Feng Y, Dubrovskaya V, Ward AB, Wyatt RT. Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design. Cell Rep. 2015;11:539–50.PubMedPubMedCentralCrossRef
60.
61.
Mao Y, Wang L, Gu C, Herschhorn A, Xiang SH, Haim H, Yang X, Sodroski J. Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer. Nat Struct Mol Biol. 2012;19:893–9.PubMedPubMedCentralCrossRef
62.
Mao Y, Wang L, Gu C, Herschhorn A, Desormeaux A, Finzi A, Xiang SH, Sodroski JG. Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer. Proc Natl Acad Sci U S A. 2013;110:12438–43.PubMedPubMedCentralCrossRef
63.
Foley B, Leitner T, Apetrei C, Hahn B, Mizrachi I, Mullins J, Rambaut A, Wolinsky S, Korber B. HIV sequence compendium. Los Alamos: Los Alamos National Laboratory, Theoretical Biology and Biophysics; 2013. p. LA-UR-13-26007.
64.
Gabuzda D, Olshevsky U, Bertani P, Haseltine WA, Sodroski J. Identification of membrane anchorage domains of the HIV-1 gp160 envelope glycoprotein precursor. J Acquir Immune Defic Syndr. 1991;4:34–40.PubMedCrossRef
65.
Haffar OK, Dowbenko DJ, Berman PW. Topogenic analysis of the human immunodeficiency virus type 1 envelope glycoprotein, gp160, in microsomal membranes. J Cell Biol. 1988;107:1677–87.PubMedCrossRef
66.
Dev J, Park D, Fu Q, Chen J, Ha HJ, Ghantous F, Herrmann T, Chang W, Liu Z, Frey G, et al. Structural basis for membrane anchoring of HIV-1 envelope spike. Science. 2016;353:172–5.PubMedPubMedCentralCrossRef
67.
Owens RJ, Burke C, Rose JK. Mutations in the membrane-spanning domain of the human immunodeficiency virus envelope glycoprotein that affect fusion activity. J Virol. 1994;68:570–4.PubMedPubMedCentral
68.
Shang L, Yue L, Hunter E. Role of the membrane-spanning domain of human immunodeficiency virus type 1 envelope glycoprotein in cell-cell fusion and virus infection. J Virol. 2008;82:5417–28.PubMedPubMedCentralCrossRef
69.
Yue L, Shang L, Hunter E. Truncation of the membrane-spanning domain of human immunodeficiency virus type 1 envelope glycoprotein defines elements required for fusion, incorporation, and infectivity. J Virol. 2009;83:11588–98.PubMedPubMedCentralCrossRef
70.
Helseth E, Olshevsky U, Gabuzda D, Ardman B, Haseltine W, Sodroski J. Changes in the transmembrane region of the human immunodeficiency virus type 1 gp41 envelope glycoprotein affect membrane fusion. J Virol. 1990;64:6314–8.PubMedPubMedCentral
71.
72.
Lovelace E, Xu H, Blish CA, Strong R, Overbaugh J. The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization. Virology. 2011;421:235–44.PubMedPubMedCentralCrossRef
73.
Ringe R, Bhattacharya J. Association of enhanced HIV-1 neutralization by a single Y681H substitution in gp41 with increased gp120-CD4 interaction and macrophage infectivity. PLoS One. 2012;7:e37157.PubMedPubMedCentralCrossRef
74.
Bradley T, Trama A, Tumba N, Gray E, Lu X, Madani N, Jahanbakhsh F, Eaton A, Xia SM, Parks R, et al. Amino acid changes in the HIV-1 gp41 membrane proximal region control virus neutralization sensitivity. EBioMedicine. 2016;12:196–207.PubMedPubMedCentralCrossRef
75.
Li Y, O’Dell S, Walker LM, Wu X, Guenaga J, Feng Y, Schmidt SD, McKee K, Louder MK, Ledgerwood JE, et al. Mechanism of neutralization by the broadly neutralizing HIV-1 monoclonal antibody VRC01. J Virol. 2011;85:8954–67.PubMedPubMedCentralCrossRef
76.
Li Y, O’Dell S, Wilson R, Wu X, Schmidt SD, Hogerkorp CM, Louder MK, Longo NS, Poulsen C, Guenaga J, et al. HIV-1 neutralizing antibodies display dual recognition of the primary and coreceptor binding sites and preferential binding to fully cleaved envelope glycoproteins. J Virol. 2012;86:11231–41.PubMedPubMedCentralCrossRef
77.
O’Rourke SM, Schweighardt B, Phung P, Mesa KA, Vollrath AL, Tatsuno GP, To B, Sinangil F, Limoli K, Wrin T, et al. Sequences in glycoprotein gp41, the CD4 binding site, and the V2 domain regulate sensitivity and resistance of HIV-1 to broadly neutralizing antibodies. J Virol. 2012;86:12105–14.PubMedPubMedCentralCrossRef
78.
O’Rourke SM, Schweighardt B, Scott WG, Wrin T, Fonseca DP, Sinangil F, Berman PW. Novel ring structure in the gp41 trimer of human immunodeficiency virus type 1 that modulates sensitivity and resistance to broadly neutralizing antibodies. J Virol. 2009;83:7728–38.PubMedPubMedCentralCrossRef
79.
Korber B, Foley BT, Kuiken C, Pillai SK, Sodroski JG. Numbering positions in HIV relative to HBX2CG. Human Retroviruses and AIDS. 1998. pp. III:102–111.
80.
Tao Y, Strelkov SV, Mesyanzhinov VV, Rossmann MG. Structure of bacteriophage T4 fibritin: a segmented coiled coil and the role of the C-terminal domain. Structure. 1997;5:789–98.PubMedCrossRef
81.
Kutner RH, Zhang XY, Reiser J. Production, concentration and titration of pseudotyped HIV-1-based lentiviral vectors. Nat Protoc. 2009;4:495–505.PubMedCrossRef
82.
Pugach P, Ozorowski G, Cupo A, Ringe R, Yasmeen A, de Val N, Derking R, Kim HJ, Korzun J, Golabek M, et al. A native-like SOSIP.664 trimer based on an HIV-1 subtype B env gene. J Virol. 2015;89:3380–95.PubMedPubMedCentralCrossRef
83.
Guenaga J, Dubrovskaya V, de Val N, Sharma SK, Carrette B, Ward AB, Wyatt RT. Structure-guided redesign increases the propensity of HIV Env to generate highly stable soluble trimers. J Virol. 2015;90:2806–17.PubMedCrossRef
84.
Bonomelli C, Doores KJ, Dunlop DC, Thaney V, Dwek RA, Burton DR, Crispin M, Scanlan CN. The glycan shield of HIV is predominantly oligomannose independently of production system or viral clade. PLoS One. 2011;6:e23521.PubMedPubMedCentralCrossRef
85.
Elbein AD, Tropea JE, Mitchell M, Kaushal GP. Kifunensine, a potent inhibitor of the glycoprotein processing mannosidase I. J Biol Chem. 1990;265:15599–605.PubMed
86.
Trkola A, Purtscher M, Muster T, Ballaun C, Buchacher A, Sullivan N, Srinivasan K, Sodroski J, Moore JP, Katinger H. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol. 1996;70:1100–8.PubMedPubMedCentral
87.
Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, Finzi A, Kwon YD, Scheid JF, Shi W, Xu L, et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science. 2010;329:811–7.PubMedPubMedCentralCrossRef
88.
Moore JP, Trkola A, Korber B, Boots LJ, Kessler JA, McCutchan FE, Mascola J, Ho DD, Robinson J, Conley AJ. A human monoclonal antibody to a complex epitope in the V3 region of gp120 of human immunodeficiency virus type 1 has broad reactivity within and outside clade B. J Virol. 1995;69:122–30.PubMedPubMedCentral
89.
Madani N, Princiotto AM, Easterhoff D, Bradley T, Luo K, Williams WB, Liao HX, Moody MA, Phad GE, Vazquez Bernat N, et al. Antibodies elicited by multiple envelope glycoprotein immunogens in primates neutralize primary human immunodeficiency viruses (HIV-1) sensitized by CD4-mimetic compounds. J Virol. 2016;90:5031–46.PubMedPubMedCentralCrossRef
90.
Thali M, Moore JP, Furman C, Charles M, Ho DD, Robinson J, Sodroski J. Characterization of conserved human immunodeficiency virus type 1 gp120 neutralization epitopes exposed upon gp120-CD4 binding. J Virol. 1993;67:3978–88.PubMedPubMedCentral
91.
Edwards TG, Wyss S, Reeves JD, Zolla-Pazner S, Hoxie JA, Doms RW, Baribaud F. Truncation of the cytoplasmic domain induces exposure of conserved regions in the ectodomain of human immunodeficiency virus type 1 envelope protein. J Virol. 2002;76:2683–91.PubMedPubMedCentralCrossRef
92.
Wyss S, Dimitrov AS, Baribaud F, Edwards TG, Blumenthal R, Hoxie JA. Regulation of human immunodeficiency virus type 1 envelope glycoprotein fusion by a membrane-interactive domain in the gp41 cytoplasmic tail. J Virol. 2005;79:12231–41.PubMedPubMedCentralCrossRef
93.
Abrahamyan LG, Mkrtchyan SR, Binley J, Lu M, Melikyan GB, Cohen FS. The cytoplasmic tail slows the folding of human immunodeficiency virus type 1 Env from a late prebundle configuration into the six-helix bundle. J Virol. 2005;79:106–15.PubMedPubMedCentralCrossRef
94.
Spies CP, Ritter Jr GD, Mulligan MJ, Compans RW. Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein alters the conformation of the external domain. J Virol. 1994;68:585–91.PubMedPubMedCentral
95.
Chen J, Kovacs JM, Peng H, Rits-Volloch S, Lu J, Park D, Zablowsky E, Seaman MS, Chen B. Effect of the cytoplasmic domain on antigenic characteristics of HIV-1 envelope glycoprotein. Science. 2015;349:191–5.PubMedPubMedCentralCrossRef
96.
Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, Wrin T, Simek MD, Fling S, Mitcham JL, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science. 2009;326:285–9.PubMedPubMedCentralCrossRef
97.
98.
McLellan JS, Pancera M, Carrico C, Gorman J, Julien JP, Khayat R, Louder R, Pejchal R, Sastry M, Dai K, et al. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature. 2011;480:336–43.PubMedPubMedCentralCrossRef
99.
Pancera M, Shahzad-Ul-Hussan S, Doria-Rose NA, McLellan JS, Bailer RT, Dai K, Loesgen S, Louder MK, Staupe RP, Yang Y, et al. Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16. Nat Struct Mol Biol. 2013;20:804–13.PubMedPubMedCentralCrossRef
100.
Pancera M, Wyatt R. Selective recognition of oligomeric HIV-1 primary isolate envelope glycoproteins by potently neutralizing ligands requires efficient precursor cleavage. Virology. 2005;332:145–56.PubMedCrossRef
101.
Si Z, Phan N, Kiprilov E, Sodroski J. Effects of HIV type 1 envelope glycoprotein proteolytic processing on antigenicity. AIDS Res Hum Retroviruses. 2003;19:217–26.PubMedCrossRef
102.
Herrera C, Klasse PJ, Michael E, Kake S, Barnes K, Kibler CW, Campbell-Gardener L, Si Z, Sodroski J, Moore JP, et al. The impact of envelope glycoprotein cleavage on the antigenicity, infectivity, and neutralization sensitivity of Env-pseudotyped human immunodeficiency virus type 1 particles. Virology. 2005;338:154–72.PubMedCrossRef
103.
Chen L, Kwon YD, Zhou T, Wu X, O’Dell S, Cavacini L, Hessell AJ, Pancera M, Tang M, Xu L, et al. Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. Science. 2009;326:1123–7.PubMedPubMedCentralCrossRef
104.
Chakrabarti BK, Pancera M, Phogat S, O’Dell S, McKee K, Guenaga J, Robinson J, Mascola J, Wyatt RT. HIV type 1 Env precursor cleavage state affects recognition by both neutralizing and nonneutralizing gp41 antibodies. AIDS Res Hum Retroviruses. 2011;27:877–87.PubMedPubMedCentralCrossRef
105.
Chakrabarti BK, Walker LM, Guenaga JF, Ghobbeh A, Poignard P, Burton DR, Wyatt RT. Direct antibody access to the HIV-1 membrane-proximal external region positively correlates with neutralization sensitivity. J Virol. 2011;85:8217–26.PubMedPubMedCentralCrossRef
106.
Haim H, Salas I, Sodroski J. Proteolytic processing of the human immunodeficiency virus envelope glycoprotein precursor decreases conformational flexibility. J Virol. 2013;87:1884–9.PubMedPubMedCentralCrossRef
107.
Yasmeen A, Ringe R, Derking R, Cupo A, Julien JP, Burton DR, Ward AB, Wilson IA, Sanders RW, Moore JP, et al. Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1Env trimers, uncleaved Env proteins, and monomeric subunits. Retrovirology. 2014;11:41.PubMedPubMedCentralCrossRef
108.
Yang X, Florin L, Farzan M, Kolchinsky P, Kwong PD, Sodroski J, Wyatt R. Modifications that stabilize human immunodeficiency virus envelope glycoprotein trimers in solution. J Virol. 2000;74:4746–54.PubMedPubMedCentralCrossRef
109.
Agrawal N, Leaman DP, Rowcliffe E, Kinkead H, Nohria R, Akagi J, Bauer K, Du SX, Whalen RG, Burton DR, et al. Functional stability of unliganded envelope glycoprotein spikes among isolates of human immunodeficiency virus type 1 (HIV-1). PLoS One. 2011;6:e21339.PubMedPubMedCentralCrossRef
110.
111.
112.
Adamian L, Nanda V, DeGrado WF, Liang J. Empirical lipid propensities of amino acid residues in multispan alpha helical membrane proteins. Proteins. 2005;59:496–509.PubMedCrossRef
Metadata
Title
Evaluation of the contribution of the transmembrane region to the ectodomain conformation of the human immunodeficiency virus (HIV-1) envelope glycoprotein
Authors
Hanh T. Nguyen
Navid Madani
Haitao Ding
Emerald Elder
Amy Princiotto
Christopher Gu
Patrice Darby
James Alin
Alon Herschhorn
John C. Kappes
Youdong Mao
Joseph G. Sodroski
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2017
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-017-0704-x

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