A structural basis for antibody-mediated neutralization of Nipah virus reveals a site of vulnerability at the fusion glycoprotein apex.
antibody response
glycoprotein
henipavirus
structure
viral fusion
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
10 12 2019
10 12 2019
Historique:
pubmed:
27
11
2019
medline:
9
4
2020
entrez:
27
11
2019
Statut:
ppublish
Résumé
Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes frequent outbreaks of severe neurologic and respiratory disease in humans with high case fatality rates. The 2 glycoproteins displayed on the surface of the virus, NiV-G and NiV-F, mediate host-cell attachment and membrane fusion, respectively, and are targets of the host antibody response. Here, we provide a molecular basis for neutralization of NiV through antibody-mediated targeting of NiV-F. Structural characterization of a neutralizing antibody (nAb) in complex with trimeric prefusion NiV-F reveals an epitope at the membrane-distal domain III (DIII) of the molecule, a region that undergoes substantial refolding during host-cell entry. The epitope of this monoclonal antibody (mAb66) is primarily protein-specific and we observe that glycosylation at the periphery of the interface likely does not inhibit mAb66 binding to NiV-F. Further characterization reveals that a Hendra virus-F-specific nAb (mAb36) and many antibodies in an antihenipavirus-F polyclonal antibody mixture (pAb835) also target this region of the molecule. Integrated with previously reported paramyxovirus F-nAb structures, these data support a model whereby the membrane-distal region of the F protein is targeted by the antibody-mediated immune response across henipaviruses. Notably, our domain-specific sequence analysis reveals no evidence of selective pressure at this region of the molecule, suggestive that functional constraints prevent immune-driven sequence variation. Combined, our data reveal the membrane-distal region of NiV-F as a site of vulnerability on the NiV surface.
Identifiants
pubmed: 31767754
pii: 1912503116
doi: 10.1073/pnas.1912503116
pmc: PMC6911215
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Viral Fusion Proteins
0
Banques de données
PDB
['6T3F']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
25057-25067Subventions
Organisme : NIAID NIH HHS
ID : R01 AI123449
Pays : United States
Organisme : Medical Research Council
ID : MR/S007555/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203141/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N00065X/1
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R01 GM093939
Pays : United States
Organisme : Medical Research Council
ID : MR/N002091/1
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : R01 AI125536
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI154739
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008169
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134384
Pays : United States
Organisme : Medical Research Council
ID : MR/L009528/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
NPJ Vaccines. 2017 Aug 8;2:21
pubmed: 29263876
J Virol. 2016 Nov 14;90(23):10762-10773
pubmed: 27654290
Nucleic Acids Res. 1988 Nov 25;16(22):10881-90
pubmed: 2849754
Trends Microbiol. 2011 Aug;19(8):389-99
pubmed: 21511478
Structure. 2007 Mar;15(3):267-73
pubmed: 17355862
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):235-42
pubmed: 21460441
J Virol. 2014 May;88(9):4624-31
pubmed: 24522928
J Mol Biol. 1996 Nov 15;263(5):800-15
pubmed: 8947577
J Virol. 2015 Feb;89(3):1838-50
pubmed: 25428863
PLoS Pathog. 2010 Jul 15;6(7):e1000993
pubmed: 20657665
J Virol. 2010 Aug;84(16):8033-41
pubmed: 20519383
Nat Rev Microbiol. 2006 Jan;4(1):23-35
pubmed: 16357858
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):355-67
pubmed: 21460454
Emerg Infect Dis. 2004 Dec;10(12):2082-7
pubmed: 15663842
PLoS Pathog. 2009 Oct;5(10):e1000642
pubmed: 19888339
Acta Crystallogr D Biol Crystallogr. 2006 Oct;62(Pt 10):1243-50
pubmed: 17001101
J Infect Dis. 2019 May 24;219(12):1867-1878
pubmed: 30364984
Curr Opin Virol. 2017 Jun;24:105-114
pubmed: 28601688
Curr Opin Virol. 2016 Feb;16:120-125
pubmed: 26978066
J Virol. 2004 Sep;78(17):9154-63
pubmed: 15308711
Virology. 2006 Mar 15;346(2):251-7
pubmed: 16460775
Nature. 2005 Jul 21;436(7049):401-5
pubmed: 16007075
Vaccine. 2015 Jun 4;33(24):2823-9
pubmed: 25865472
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W375-83
pubmed: 17452350
Arch Virol. 2012 Sep;157(9):1635-41
pubmed: 22669317
PLoS Pathog. 2013;9(11):e1003770
pubmed: 24278018
Microbes Infect. 2002 Feb;4(2):145-51
pubmed: 11880045
Curr Top Microbiol Immunol. 2012;359:25-40
pubmed: 22752412
Proc Natl Acad Sci U S A. 2013 Sep 17;110(38):E3544-6
pubmed: 23929778
J Infect Dis. 2013 Feb 1;207(3):469-78
pubmed: 23175762
MBio. 2013 Jul 02;4(4):null
pubmed: 23820396
Mol Biol Evol. 2007 Aug;24(8):1586-91
pubmed: 17483113
Cell Rep. 2018 Dec 26;25(13):3750-3758.e4
pubmed: 30590046
Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):1056-61
pubmed: 26712026
PLoS Pathog. 2013;9(10):e1003684
pubmed: 24130486
PLoS Negl Trop Dis. 2019 Jun 6;13(6):e0007462
pubmed: 31170144
J Virol. 2007 May;81(9):4520-32
pubmed: 17301148
J Gen Virol. 2000 Aug;81(Pt 8):1927-32
pubmed: 10900029
Indian J Med Res. 2006 Apr;123(4):553-60
pubmed: 16783047
Mol Biol Evol. 2015 May;32(5):1365-71
pubmed: 25701167
Virology. 2015 May;479-480:518-31
pubmed: 25771804
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12265-12270
pubmed: 30420505
PLoS Pathog. 2015 Dec 08;11(12):e1005322
pubmed: 26646856
Sci Transl Med. 2014 Jun 25;6(242):242ra82
pubmed: 24964990
Nature. 2006 Jan 5;439(7072):38-44
pubmed: 16397490
Acta Crystallogr D Biol Crystallogr. 2005 Jun;61(Pt 6):651-7
pubmed: 15930615
J Virol. 2012 Nov;86(21):11457-71
pubmed: 22915804
J Biol Chem. 2009 Jan 16;284(3):1628-35
pubmed: 19019819
Virology. 2008 Jun 5;375(2):391-400
pubmed: 18342904
J Mol Biol. 2007 Sep 21;372(3):774-97
pubmed: 17681537
Vaccine. 2014 May 7;32(22):2637-44
pubmed: 24631094
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Science. 2000 May 26;288(5470):1432-5
pubmed: 10827955
J Virol. 2013 Sep;87(18):10221-31
pubmed: 23864637
Mol Biol Evol. 2013 May;30(5):1196-205
pubmed: 23420840
PLoS Pathog. 2006 Feb;2(2):e7
pubmed: 16477309
Curr Opin Virol. 2014 Apr;5:24-33
pubmed: 24530984
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Mol Biol Evol. 2016 Nov;33(11):2836-2847
pubmed: 27512112
Nat Commun. 2012 Apr 24;3:796
pubmed: 22531181
J Virol. 2004 Jan;78(2):834-40
pubmed: 14694115
J Virol. 2011 Jun;85(12):5940-8
pubmed: 21450814
Virol J. 2009 Jul 31;6:119
pubmed: 19646266
J Virol. 2006 Feb;80(4):1972-8
pubmed: 16439553
Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):7320-7325
pubmed: 29941589
Curr Opin Struct Biol. 2007 Aug;17(4):427-36
pubmed: 17870467
Biochem Soc Trans. 2010 Oct;38(5):1349-55
pubmed: 20863312
Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):E2156-65
pubmed: 25825759
Cell Rep. 2016 Aug 30;16(9):2327-38
pubmed: 27545891
MBio. 2015 Feb 17;6(1):e02393-14
pubmed: 25691596
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Viruses. 2016 Apr 21;8(4):109
pubmed: 27110809
Lancet. 1999 Oct 9;354(9186):1253-6
pubmed: 10520634
Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9288-93
pubmed: 15964978
Science. 1995 Apr 7;268(5207):94-7
pubmed: 7701348
J Virol. 2006 May;80(10):4878-89
pubmed: 16641279
Cell Rep. 2015 Jun 9;11(9):1331-8
pubmed: 26004185
Curr Top Microbiol Immunol. 2012;359:59-78
pubmed: 22695915
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4
pubmed: 24753421
J Virol. 2012 Jun;86(12):6632-42
pubmed: 22496210