Lack of correlation between soluble CD4-induced shedding of the human immunodeficiency virus type 1 exterior envelope glycoprotein and subsequent membrane fusion events - PubMed (original) (raw)
Lack of correlation between soluble CD4-induced shedding of the human immunodeficiency virus type 1 exterior envelope glycoprotein and subsequent membrane fusion events
M Thali et al. J Virol. 1992 Sep.
Abstract
The noncovalent association of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) is disrupted by soluble CD4 binding, resulting in shedding of the gp120 exterior envelope glycoprotein. This observation has led to the speculation that interaction of gp120 with the CD4 receptor triggers shedding of the exterior envelope glycoprotein, allowing exposure of gp41 domains necessary for membrane fusion steps involved in virus entry or syncytium formation. To test this hypothesis, a set of HIV-1 envelope glycoprotein mutants were used to examine the relationship of soluble CD4-induced shedding of the gp120 glycoprotein to envelope glycoprotein function in syncytium formation and virus entry. All mutants with a threefold or greater reduction in CD4-binding ability exhibited marked decreases in gp120 shedding in response to soluble CD4, even though several of these mutants exhibited significant levels of envelope glycoprotein function. Conversely, most fusion-defective mutants with wild-type gp120-CD4 binding affinity, including those with changes in the V3 loop, efficiently shed gp120 following soluble CD4 binding. Thus, soluble CD4-induced shedding of gp120 is not a generally useful marker for conformational changes in the HIV-1 envelope glycoproteins necessary for the virus entry or syncytium formation processes. Some gp120 mutants, despite being expressed on the cell surface and capable of efficiently binding soluble CD4, exhibited decreased gp120 shedding. These mutants were still sensitive to neutralization by soluble CD4, indicating that, for envelope glycoproteins exhibiting high affinity for soluble CD4, competitive inhibition may be more important than gp120 shedding for the antiviral effect.
Similar articles
- Characterization of Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Variants Selected for Resistance to a CD4-Mimetic Compound.
Anang S, Richard J, Bourassa C, Goyette G, Chiu TJ, Chen HC, Smith AB 3rd, Madani N, Finzi A, Sodroski J. Anang S, et al. J Virol. 2022 Sep 14;96(17):e0063622. doi: 10.1128/jvi.00636-22. Epub 2022 Aug 18. J Virol. 2022. PMID: 35980207 Free PMC article. - Activation and Inactivation of Primary Human Immunodeficiency Virus Envelope Glycoprotein Trimers by CD4-Mimetic Compounds.
Madani N, Princiotto AM, Zhao C, Jahanbakhshsefidi F, Mertens M, Herschhorn A, Melillo B, Smith AB 3rd, Sodroski J. Madani N, et al. J Virol. 2017 Jan 18;91(3):e01880-16. doi: 10.1128/JVI.01880-16. Print 2017 Feb 1. J Virol. 2017. PMID: 27881646 Free PMC article. - Functional and immunologic characterization of human immunodeficiency virus type 1 envelope glycoproteins containing deletions of the major variable regions.
Wyatt R, Sullivan N, Thali M, Repke H, Ho D, Robinson J, Posner M, Sodroski J. Wyatt R, et al. J Virol. 1993 Aug;67(8):4557-65. doi: 10.1128/JVI.67.8.4557-4565.1993. J Virol. 1993. PMID: 8331723 Free PMC article. - CD4 activation of HIV fusion.
Sattentau QJ. Sattentau QJ. Int J Cell Cloning. 1992 Nov;10(6):323-32. doi: 10.1002/stem.5530100603. Int J Cell Cloning. 1992. PMID: 1281202 Review. - Structure-based design, synthesis and validation of CD4-mimetic small molecule inhibitors of HIV-1 entry: conversion of a viral entry agonist to an antagonist.
Courter JR, Madani N, Sodroski J, Schön A, Freire E, Kwong PD, Hendrickson WA, Chaiken IM, LaLonde JM, Smith AB 3rd. Courter JR, et al. Acc Chem Res. 2014 Apr 15;47(4):1228-37. doi: 10.1021/ar4002735. Epub 2014 Feb 6. Acc Chem Res. 2014. PMID: 24502450 Free PMC article. Review.
Cited by
- HIV-1 Entry and Membrane Fusion Inhibitors.
Xiao T, Cai Y, Chen B. Xiao T, et al. Viruses. 2021 Apr 23;13(5):735. doi: 10.3390/v13050735. Viruses. 2021. PMID: 33922579 Free PMC article. Review. - Immunogenicity of HIV-1-Based Virus-Like Particles with Increased Incorporation and Stability of Membrane-Bound Env.
Gonelli CA, King HAD, Mackenzie C, Sonza S, Center RJ, Purcell DFJ. Gonelli CA, et al. Vaccines (Basel). 2021 Mar 10;9(3):239. doi: 10.3390/vaccines9030239. Vaccines (Basel). 2021. PMID: 33801906 Free PMC article. - Molecular Mechanism of HIV-1 Entry.
Chen B. Chen B. Trends Microbiol. 2019 Oct;27(10):878-891. doi: 10.1016/j.tim.2019.06.002. Epub 2019 Jun 28. Trends Microbiol. 2019. PMID: 31262533 Free PMC article. Review. - Structural basis of coreceptor recognition by HIV-1 envelope spike.
Shaik MM, Peng H, Lu J, Rits-Volloch S, Xu C, Liao M, Chen B. Shaik MM, et al. Nature. 2019 Jan;565(7739):318-323. doi: 10.1038/s41586-018-0804-9. Epub 2018 Dec 12. Nature. 2019. PMID: 30542158 Free PMC article. - HIV-1 Escape from a Peptidic Anchor Inhibitor through Stabilization of the Envelope Glycoprotein Spike.
Eggink D, de Taeye SW, Bontjer I, Klasse PJ, Langedijk JPM, Berkhout B, Sanders RW. Eggink D, et al. J Virol. 2016 Nov 14;90(23):10587-10599. doi: 10.1128/JVI.01616-16. Print 2016 Dec 1. J Virol. 2016. PMID: 27654295 Free PMC article.
References
- Nature. 1988 Jan 7;331(6151):84-6 - PubMed
- Science. 1985 May 3;228(4699):593-5 - PubMed
- Science. 1986 Jan 24;231(4736):382-5 - PubMed
- Cell. 1986 Nov 7;47(3):333-48 - PubMed
- Nature. 1988 Jan 7;331(6151):82-4 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials