Antibody escape by polyomavirus capsid mutation facilitates neurovirulence.
Cryo EM
fab:capsid complex
immunology
inflammation
mouse
neutralizing antibody
polyomavirus
progressive multifocal leukoencephalopathy
subvolume refinement
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
17 09 2020
17 09 2020
Historique:
received:
14
07
2020
accepted:
17
09
2020
pubmed:
18
9
2020
medline:
20
2
2021
entrez:
17
9
2020
Statut:
epublish
Résumé
JCPyV polyomavirus, a member of the human virome, causes progressive multifocal leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. Mutations in the major viral capsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape from virus-neutralizing antibody (nAb) in vivo is unknown. A mouse polyomavirus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a major reservoir for JCPyV persistence, but retained the CNS infectivity, cell tropism, and neuropathology of the parental virus. This mutation rendered MuPyV resistant to a monoclonal Ab (mAb), whose specificity overlapped the endogenous anti-VP1 response. Using cryo-EM and a custom sub-particle refinement approach, we resolved an MuPyV:Fab complex map to 3.2 Å resolution. The structure revealed the mechanism of mAb evasion. Our findings demonstrate convergence between nAb evasion and CNS neurovirulence in vivo by a frequent JCPyV-PML VP1 mutation.
Identifiants
pubmed: 32940605
doi: 10.7554/eLife.61056
pii: 61056
pmc: PMC7541085
doi:
pii:
Substances chimiques
Antibodies, Monoclonal
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS092662
Pays : United States
Organisme : NINDS NIH HHS
ID : F32 NS106730
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA060395
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS083336
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS088367
Pays : United States
Informations de copyright
© 2020, Lauver et al.
Déclaration de conflit d'intérêts
ML, DG, CN, KA, GJ, DH, EF, SC, CB, SB, NC, SH, AL No competing interests declared
Références
J Virol. 2010 Oct;84(20):10448-56
pubmed: 20686041
J Neurovirol. 2003;9 Suppl 1:81-7
pubmed: 12709877
Blood. 2009 May 14;113(20):4834-40
pubmed: 19264918
J Virol. 1999 Jul;73(7):5826-32
pubmed: 10364334
PLoS Pathog. 2018 Jan 25;14(1):e1006825
pubmed: 29370298
J Neurovirol. 2000 Oct;6(5):398-409
pubmed: 11031693
Cell. 2009 Jul 10;138(1):30-50
pubmed: 19596234
Nat Commun. 2015 Nov 04;6:8843
pubmed: 26534841
J Virol. 2018 Mar 28;92(8):
pubmed: 29437972
J Virol. 2020 Mar 31;94(8):
pubmed: 31996425
Nat Neurosci. 2010 Jun;13(6):700-7
pubmed: 20473291
Cell. 2019 Sep 5;178(6):1277-1279
pubmed: 31474369
Cell Host Microbe. 2020 Feb 12;27(2):249-261.e5
pubmed: 32027857
PLoS One. 2018 Oct 23;13(10):e0206273
pubmed: 30352098
J Infect Dis. 2011 Jul 1;204(1):103-14
pubmed: 21628664
JAMA Neurol. 2017 Apr 1;74(4):437-444
pubmed: 28241186
Curr Opin Struct Biol. 2018 Oct;52:25-31
pubmed: 30096461
J Virol. 1995 May;69(5):3167-70
pubmed: 7707545
PLoS Pathog. 2015 Oct 16;11(10):e1005104
pubmed: 26474293
Structure. 1996 Feb 15;4(2):183-94
pubmed: 8805524
J Neurovirol. 2019 Aug;25(4):520-524
pubmed: 31025264
Nat Commun. 2018 Dec 14;9(1):5326
pubmed: 30552337
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
J Virol. 2010 May;84(9):4243-51
pubmed: 20181697
J Virol. 2010 Oct;84(19):9840-52
pubmed: 20668088
Virology. 2007 Jul 20;364(1):55-63
pubmed: 17399760
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
IUCrJ. 2020 Feb 11;7(Pt 2):253-267
pubmed: 32148853
N Engl J Med. 2005 Jul 28;353(4):362-8
pubmed: 15947080
Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2749-54
pubmed: 10688894
N Engl J Med. 2005 Jul 28;353(4):369-74
pubmed: 15947079
Immunity. 2019 Mar 19;50(3):668-676.e5
pubmed: 30824324
J Struct Biol. 2009 May;166(2):234-40
pubmed: 19236920
J Immunol. 2012 May 1;188(9):4340-8
pubmed: 22447978
Curr Biol. 1998 Mar 26;8(7):377-85
pubmed: 9545195
J Am Acad Dermatol. 2011 Sep;65(3):546-551
pubmed: 21514689
Development. 2011 Dec;138(24):5291-300
pubmed: 22071110
Structure. 2018 Jun 5;26(6):839-847.e3
pubmed: 29706532
Am J Transplant. 2006 May;6(5 Pt 1):913-22
pubmed: 16611327
Sci Transl Med. 2015 Sep 23;7(306):306ra151
pubmed: 26400912
J Gen Virol. 2010 Dec;91(Pt 12):3042-52
pubmed: 20826618
Sci Rep. 2018 Dec 24;8(1):18070
pubmed: 30584239
Cold Spring Harb Symp Quant Biol. 1962;27:1-24
pubmed: 14019094
Science. 2009 Oct 30;326(5953):734-6
pubmed: 19900932
Prog Biophys Mol Biol. 2020 May 26;:
pubmed: 32470354
mBio. 2013 Jun 11;4(3):e00247-13
pubmed: 23760462
Structure. 2016 Apr 5;24(4):528-536
pubmed: 26996963
J Exp Med. 1996 Feb 1;183(2):403-11
pubmed: 8627153
J Neurovirol. 2004 Feb;10(1):1-11
pubmed: 14982723
Annu Rev Virol. 2017 Sep 29;4(1):349-367
pubmed: 28637388
J Immunol Methods. 1986 Jan 22;86(1):83-7
pubmed: 3944471
Am J Pathol. 1987 May;127(2):243-61
pubmed: 2437801
Sci Transl Med. 2015 Sep 23;7(306):306ra150
pubmed: 26400911
Cell Host Microbe. 2010 Oct 21;8(4):309-19
pubmed: 20951965
N Engl J Med. 1988 Feb 4;318(5):301-5
pubmed: 2827029
J Virol. 2004 Sep;78(18):10206-10
pubmed: 15331755
Nat Rev Neurosci. 2009 Feb;10(2):153-63
pubmed: 19153578
mSphere. 2017 Nov 15;2(6):
pubmed: 29152583
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
J Immunol Methods. 2000 Jan 13;233(1-2):167-77
pubmed: 10648866
Ann Intern Med. 1987 Jul;107(1):78-87
pubmed: 3296901
Sci Transl Med. 2015 Dec 23;7(319):319ra206
pubmed: 26702094
J Virol. 2009 Jun;83(11):5556-66
pubmed: 19321620
Virology. 2015 Sep;483:253-63
pubmed: 25996608
Nat Commun. 2018 Apr 19;9(1):1552
pubmed: 29674632
EMBO J. 1997 Aug 15;16(16):5139-48
pubmed: 9305654
N Engl J Med. 2005 Jul 28;353(4):375-81
pubmed: 15947078
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
Cell Host Microbe. 2018 Nov 14;24(5):717-730.e5
pubmed: 30439341
Ann Neurol. 1985 Apr;17(4):344-9
pubmed: 4004155
Nature. 1991 Apr 4;350(6317):423-6
pubmed: 1901381
Virology. 2010 Jun 20;402(1):164-76
pubmed: 20381826
Elife. 2018 Nov 09;7:
pubmed: 30412051
Methods Enzymol. 2016;579:1-17
pubmed: 27572721
Nature. 2003 Mar 20;422(6929):307-12
pubmed: 12646921
Eur J Immunol. 1982 Jan;12(1):60-9
pubmed: 6977452
Nucleic Acids Res. 2018 Jul 2;46(W1):W296-W303
pubmed: 29788355
Brain. 1958 Mar;81(1):93-111
pubmed: 13523006
Nature. 2015 Jul 9;523(7559):217-20
pubmed: 26053121
Ann Neurol. 2014 Jul;76(1):140-7
pubmed: 24895208
J Gen Virol. 2003 Nov;84(Pt 11):2927-2936
pubmed: 14573797
Cell Rep. 2017 Oct 31;21(5):1169-1179
pubmed: 29091757
Hepatology. 2015 Mar;61(3):823-33
pubmed: 25418031
Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):8017-8022
pubmed: 28696310
PLoS Genet. 2009 Feb;5(2):e1000368
pubmed: 19197354
J Infect Dis. 2011 Jul 15;204(2):237-44
pubmed: 21673034
Virology. 1998 Dec 5;252(1):275-84
pubmed: 9875336
J Virol. 2015 Jan 15;89(2):1340-7
pubmed: 25392214
Nat Rev Microbiol. 2018 Jan;16(1):60
pubmed: 29109554
J Immunol. 1998 Feb 15;160(4):1724-34
pubmed: 9469430
PLoS Pathog. 2020 Mar 4;16(3):e1008371
pubmed: 32130281
N Engl J Med. 2013 Sep 26;369(13):1280
pubmed: 24066761
J Clin Invest. 2014 Dec;124(12):5323-36
pubmed: 25401469
J Struct Biol. 2017 Dec;200(3):244-247
pubmed: 28559165
Adv Virus Res. 2019;105:73-91
pubmed: 31522709
Neurology. 2012 Feb 14;78(7):458-67; discussion 465
pubmed: 22302546
J Gen Virol. 2005 Jul;86(Pt 7):2035-2045
pubmed: 15958683
Clin Vaccine Immunol. 2011 Oct;18(10):1737-43
pubmed: 21880855