Networks of HIV-1 Envelope Glycans Maintain Antibody Epitopes in the Face of Glycan Additions and Deletions.
Antibodies, Monoclonal
/ chemistry
Antigen-Antibody Complex
/ chemistry
Broadly Neutralizing Antibodies
/ chemistry
Epitopes
/ chemistry
HEK293 Cells
HIV Antibodies
/ chemistry
HIV-1
/ immunology
Humans
Molecular Docking Simulation
Mutation
Polysaccharides
/ chemistry
env Gene Products, Human Immunodeficiency Virus
/ chemistry
broadly neutralizing antibodies
cryo-electron microscopy
glycans
glycosylation
human immunodeficiency virus
mass spectrometry
structure
vaccines
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
04 08 2020
04 08 2020
Historique:
received:
13
05
2019
revised:
27
02
2020
accepted:
28
04
2020
pubmed:
21
5
2020
medline:
29
7
2021
entrez:
21
5
2020
Statut:
ppublish
Résumé
Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike. Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans. Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets. Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network. In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans. Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.
Identifiants
pubmed: 32433992
pii: S0969-2126(20)30168-4
doi: 10.1016/j.str.2020.04.022
pmc: PMC7416112
pii:
doi:
Substances chimiques
2G12 monoclonal antibody
0
Antibodies, Monoclonal
0
Antigen-Antibody Complex
0
Broadly Neutralizing Antibodies
0
Epitopes
0
HIV Antibodies
0
Polysaccharides
0
env Gene Products, Human Immunodeficiency Virus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
897-909.e6Subventions
Organisme : NIAID NIH HHS
ID : F31 AI131873
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI110657
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The International AIDS Vaccine Initiative (IAVI) has previously filed a patent relating to the BG505 SOSIP.664 trimer: US Prov. Appln. no. 61/772,739, entitled “HIV-1 Envelope Glycoprotein,” with R.W.S. and A.B.W. among the co-inventors, but no patents have been filed on any work described here.
Références
J Virol. 2019 Feb 5;93(4):
pubmed: 30487280
Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13372-7
pubmed: 16174734
Protein Sci. 2018 Jan;27(1):293-315
pubmed: 29067766
J Virol. 1996 Feb;70(2):1100-8
pubmed: 8551569
PLoS Pathog. 2013 Jan;9(1):e1003106
pubmed: 23300456
Science. 2003 Jun 27;300(5628):2065-71
pubmed: 12829775
Science. 2013 May 10;340(6133):711-6
pubmed: 23539181
J Exp Med. 2017 Sep 4;214(9):2573-2590
pubmed: 28847869
J Virol. 2004 Nov;78(22):12625-37
pubmed: 15507649
Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13800-5
pubmed: 20643940
Acta Crystallogr D Struct Biol. 2018 Apr 1;74(Pt 4):256-263
pubmed: 29652253
J Virol. 2015 Jul;89(13):6952-9
pubmed: 25878100
J Virol. 2017 Jan 3;91(2):
pubmed: 27807235
Structure. 2019 Jan 2;27(1):134-139.e3
pubmed: 30344107
Virology. 2017 May;505:193-209
pubmed: 28279830
Cell Rep. 2018 Oct 23;25(4):893-908.e7
pubmed: 30355496
J Struct Biol. 1999 Dec 1;128(1):82-97
pubmed: 10600563
Annu Rev Biophys. 2018 May 20;47:499-523
pubmed: 29595997
Nat Struct Mol Biol. 2015 Nov;22(11):833-4
pubmed: 26581513
J Virol. 2009 Jul;83(14):7337-48
pubmed: 19439467
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Nature. 2014 Nov 6;515(7525):138-42
pubmed: 25186731
J Struct Biol. 2016 Jan;193(1):1-12
pubmed: 26592709
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Immunity. 2014 May 15;40(5):669-80
pubmed: 24768348
J Virol. 2014 Sep 1;88(17):10177-88
pubmed: 24965454
Immunity. 2014 May 15;40(5):657-68
pubmed: 24768347
Biochem Biophys Res Commun. 2009 Dec 18;390(3):404-9
pubmed: 19748484
J Virol. 2016 Nov 28;90(24):11132-11144
pubmed: 27707925
Science. 2011 Nov 25;334(6059):1097-103
pubmed: 21998254
Trends Microbiol. 2014 Oct;22(10):550-1
pubmed: 25169020
Science. 2011 Sep 16;333(6049):1593-602
pubmed: 21835983
Nat Struct Mol Biol. 2016 Oct;23(10):906-915
pubmed: 27617431
Nat Struct Mol Biol. 2013 Jul;20(7):796-803
pubmed: 23708606
Nat Methods. 2015 Oct;12(10):943-6
pubmed: 26280328
Nat Commun. 2018 Sep 12;9(1):3693
pubmed: 30209313
Science. 1998 Jun 19;280(5371):1884-8
pubmed: 9632381
Cell Rep. 2017 Aug 22;20(8):1805-1817
pubmed: 28834745
Immunol Rev. 2017 Jan;275(1):161-182
pubmed: 28133806
Nat Methods. 2015 Apr;12(4):361-365
pubmed: 25707030
Nat Commun. 2017 Mar 28;8:14954
pubmed: 28348411
J Virol. 2002 Jul;76(14):7293-305
pubmed: 12072528
Proteins. 2015 Mar;83(3):590-6
pubmed: 25546301
J Virol. 2002 Jul;76(14):7306-21
pubmed: 12072529
Structure. 2015 Oct 6;23(10):1943-1951
pubmed: 26388028
Retrovirology. 2008 Jan 31;5:10
pubmed: 18237398
Expert Rev Proteomics. 2017 Oct;14(10):881-890
pubmed: 28870097
Immunity. 2017 Sep 19;47(3):524-537.e3
pubmed: 28916265
AIDS Res Hum Retroviruses. 1990 May;6(5):567-79
pubmed: 1694449
Immunol Rev. 2017 Jan;275(1):296-312
pubmed: 28133803
Cell. 2016 May 5;165(4):813-26
pubmed: 27114034
Science. 2009 Oct 9;326(5950):285-9
pubmed: 19729618
Curr HIV/AIDS Rep. 2016 Feb;13(1):31-7
pubmed: 26841901
Science. 2012 Jul 13;337(6091):183-6
pubmed: 22798606
J Proteome Res. 2018 Mar 2;17(3):987-999
pubmed: 29420040
Nat Commun. 2015 Jun 24;6:7479
pubmed: 26105115
AIDS. 2009 Nov 27;23(18):2405-14
pubmed: 19770692
Nature. 2011 Nov 23;480(7377):336-43
pubmed: 22113616
Cell Rep. 2017 Oct 3;21(1):222-235
pubmed: 28978475
PLoS Pathog. 2018 Feb 23;14(2):e1006913
pubmed: 29474444
PLoS Pathog. 2013 Sep;9(9):e1003618
pubmed: 24068931
J Immunol. 1991 Jun 15;146(12):4325-32
pubmed: 1710248
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D242-6
pubmed: 15608187
J Virol. 2010 Oct;84(20):10690-9
pubmed: 20702629
PLoS Pathog. 2015 Aug 12;11(8):e1005110
pubmed: 26267277
Nat Struct Mol Biol. 2013 Jul;20(7):804-13
pubmed: 23708607
Structure. 2019 Jan 2;27(1):196-206.e6
pubmed: 30471922
Biotechnol Bioeng. 2018 Apr;115(4):885-899
pubmed: 29150937
Nature. 2003 Mar 20;422(6929):307-12
pubmed: 12646921
PLoS Pathog. 2011 Sep;7(9):e1002200
pubmed: 21909262
Immunity. 2016 Sep 20;45(3):483-496
pubmed: 27617678
Nucleic Acids Res. 2015 Jul 1;43(W1):W314-9
pubmed: 25908787
PLoS One. 2011;6(8):e23521
pubmed: 21858152
Immunol Rev. 2017 Jan;275(1):203-216
pubmed: 28133796
J Virol. 2013 Feb;87(4):2234-41
pubmed: 23221565
J Exp Med. 2013 Apr 8;210(4):655-63
pubmed: 23530120
Cell Rep. 2015 Jun 16;11(10):1604-13
pubmed: 26051934
Glycobiology. 2010 Jul;20(7):812-23
pubmed: 20181792
Cell Rep. 2018 Aug 21;24(8):1958-1966.e5
pubmed: 30134158
Retrovirology. 2013 Feb 06;10:14
pubmed: 23384254
J Struct Biol. 2000 Oct;132(1):33-45
pubmed: 11121305
PLoS Pathog. 2016 Sep 14;12(9):e1005864
pubmed: 27627672
Cell Rep. 2016 Aug 30;16(9):2327-38
pubmed: 27545891
J Proteome Res. 2013 Mar 1;12(3):1223-34
pubmed: 23339644
Cell. 2015 Dec 17;163(7):1702-15
pubmed: 26687358
Cell Rep. 2016 Mar 22;14(11):2695-706
pubmed: 26972002
J Virol. 2010 Oct;84(20):10510-21
pubmed: 20686044
Cell Rep. 2014 May 8;7(3):785-95
pubmed: 24767986
J Virol. 2019 Sep 30;93(20):
pubmed: 31375582
Curr Opin Struct Biol. 2017 Jun;44:125-133
pubmed: 28363124
Nature. 2011 Sep 22;477(7365):466-70
pubmed: 21849977
J Virol. 2014 Mar;88(5):2645-57
pubmed: 24352455
Immunol Rev. 2017 Jan;275(1):21-32
pubmed: 28133813
PLoS Pathog. 2015 May 29;11(5):e1004932
pubmed: 26023780
Cold Spring Harb Perspect Biol. 2017 Nov 1;9(11):
pubmed: 28159875
Nat Med. 2012 Nov;18(11):1688-92
pubmed: 23086475
Nature. 2007 Apr 26;446(7139):1038-45
pubmed: 17460665
Science. 2010 Aug 13;329(5993):856-61
pubmed: 20616233
Structure. 2017 Oct 3;25(10):1631-1639.e2
pubmed: 28890362