An Evolutionary Insertion in the Mxra8 Receptor-Binding Site Confers Resistance to Alphavirus Infection and Pathogenesis.
Amino Acid Sequence
Animals
Binding Sites
Cattle
/ genetics
Chikungunya Fever
/ genetics
Chikungunya virus
Chlorocebus aethiops
Disease Resistance
Evolution, Molecular
Female
Gene Knock-In Techniques
HEK293 Cells
Humans
Immunoglobulins
/ genetics
Membrane Proteins
/ chemistry
Mice
Mice, Inbred C57BL
Molecular Docking Simulation
NIH 3T3 Cells
Protein Domains
Receptors, Virus
/ chemistry
Vero Cells
Bovinae
X-ray crystallography
alphavirus
evolution
infection
pathogenesis
receptor
Journal
Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316
Informations de publication
Date de publication:
11 03 2020
11 03 2020
Historique:
received:
21
10
2019
revised:
11
12
2019
accepted:
14
01
2020
pubmed:
23
2
2020
medline:
24
3
2020
entrez:
21
2
2020
Statut:
ppublish
Résumé
Alphaviruses are emerging, mosquito-transmitted RNA viruses with poorly understood cellular tropism and species selectivity. Mxra8 is a receptor for multiple alphaviruses including chikungunya virus (CHIKV). We discovered that while expression of mouse, rat, chimpanzee, dog, horse, goat, sheep, and human Mxra8 enables alphavirus infection in cell culture, cattle Mxra8 does not. Cattle Mxra8 encodes a 15-amino acid insertion in its ectodomain that prevents Mxra8 binding to CHIKV. Identical insertions are present in zebu, yak, and the extinct auroch. As other Bovinae lineages contain related Mxra8 sequences, this insertion likely occurred at least 5 million years ago. Removing the Mxra8 insertion in Bovinae enhances alphavirus binding and infection, while introducing the insertion into mouse Mxra8 blocks CHIKV binding, prevents infection by multiple alphaviruses in cells, and mitigates CHIKV-induced pathogenesis in mice. Our studies on how this insertion provides resistance to CHIKV infection could facilitate countermeasures that disrupt Mxra8 interactions with alphaviruses.
Identifiants
pubmed: 32075743
pii: S1931-3128(20)30047-0
doi: 10.1016/j.chom.2020.01.008
pmc: PMC7163869
mid: NIHMS1569141
pii:
doi:
Substances chimiques
Immunoglobulins
0
Membrane Proteins
0
Mxra8 protein, mouse
0
Receptors, 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
428-440.e9Subventions
Organisme : NIAID NIH HHS
ID : R01 AI123348
Pays : United States
Organisme : NHGRI NIH HHS
ID : U41 HG010972
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG007175
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI089591
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI095436
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA200060
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007172
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI114816
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG008345
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143673
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142790
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201700060C
Pays : United States
Organisme : NIEHS NIH HHS
ID : U24 ES026699
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests M.S.D. is a consultant for Inbios and Emergent BioSolutions and is on the scientific advisory board of Moderna. D.H.F. is a founder of Courier Therapeutics.
Références
Nat Rev Rheumatol. 2012 May 08;8(7):420-9
pubmed: 22565316
Mol Phylogenet Evol. 2019 Apr;133:256-262
pubmed: 30562611
N Z Vet J. 2009 Apr;57(2):116-20
pubmed: 19471331
Inflamm Bowel Dis. 2019 Apr 11;25(5):853-861
pubmed: 30534988
Cell. 2015 Nov 19;163(5):1095-1107
pubmed: 26553503
Vet Microbiol. 1988 Oct;18(2):109-18
pubmed: 3218073
Vet J. 1999 Mar;157(2):123-38
pubmed: 10204408
Cell. 1995 Feb 24;80(4):621-30
pubmed: 7867069
Cell. 2001 Apr 6;105(1):137-48
pubmed: 11301009
Glia. 2003 Dec;44(3):190-204
pubmed: 14603461
J Virol. 1995 Mar;69(3):1621-7
pubmed: 7853497
Nature. 2018 May;557(7706):570-574
pubmed: 29769725
Gene. 2004 Apr 14;330:85-92
pubmed: 15087127
Arch Virol Suppl. 1994;9:473-84
pubmed: 7913360
Antiviral Res. 2012 Jun;94(3):242-57
pubmed: 22522323
J Mol Evol. 1985;22(2):160-74
pubmed: 3934395
Mol Biol Evol. 2011 Feb;28(2):899-909
pubmed: 20943830
Syst Biol. 2016 Jul;65(4):726-36
pubmed: 27235697
J Mol Evol. 2004 Apr;58(4):460-5
pubmed: 15114424
Cardiovasc Res. 2013 Apr 1;98(1):73-82
pubmed: 23386276
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
Genome Res. 2013 May;23(5):749-61
pubmed: 23478400
Trans R Soc Trop Med Hyg. 1996 Jan-Feb;90(1):31-3
pubmed: 8730305
BMC Genomics. 2009 Apr 24;10:177
pubmed: 19393045
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21
pubmed: 20057044
EMBO J. 1998 Aug 17;17(16):4585-93
pubmed: 9707418
Virology. 1993 Nov;197(1):375-90
pubmed: 8105605
J Virol. 1997 Feb;71(2):1558-66
pubmed: 8995682
Cell Rep. 2019 Sep 3;28(10):2647-2658.e5
pubmed: 31484075
J Virol. 1996 Mar;70(3):2069-73
pubmed: 8627739
Nature. 2010 Dec 2;468(7324):709-12
pubmed: 21124458
Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16026-31
pubmed: 21896745
J Virol. 2011 Sep;85(18):9327-33
pubmed: 21752915
Osteoarthritis Cartilage. 2018 Jul;26(7):945-953
pubmed: 29702220
Nat Genet. 1997 May;16(1):100-3
pubmed: 9140404
Nature. 2015 Feb 19;518(7539):317-30
pubmed: 25693563
Cell. 2019 Jun 13;177(7):1714-1724.e12
pubmed: 31080063
PLoS Negl Trop Dis. 2013;7(2):e2050
pubmed: 23409203
J Mol Evol. 1994 Sep;39(3):306-14
pubmed: 7932792
J Exp Med. 2019 Oct 7;216(10):2282-2301
pubmed: 31337735
Commun Biol. 2018 Oct 19;1:169
pubmed: 30374461
PLoS Biol. 2013;11(5):e1001571
pubmed: 23723737
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Virology. 2005 Feb 20;332(2):511-8
pubmed: 15680416
Cell Host Microbe. 2011 Aug 18;10(2):97-104
pubmed: 21843867
Nucleic Acids Res. 2014 Nov 10;42(20):12367-79
pubmed: 25336616
Bioinformatics. 2009 May 1;25(9):1189-91
pubmed: 19151095
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Am J Trop Med Hyg. 2016 Mar;94(3):504-6
pubmed: 26666699
J Gen Virol. 2006 Sep;87(Pt 9):2467-2476
pubmed: 16894184
Nucleic Acids Res. 2016 Jan 4;44(D1):D834-9
pubmed: 26481361
J Virol. 1998 Sep;72(9):7357-66
pubmed: 9696832
Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9095-9
pubmed: 8415660
J Virol. 1992 Aug;66(8):4992-5001
pubmed: 1385835
J Bone Miner Res. 2012 Sep;27(9):2024-34
pubmed: 22492581
Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10648-52
pubmed: 7479858
Cell. 2019 Jun 13;177(7):1725-1737.e16
pubmed: 31080061
J Biol Chem. 2017 Feb 10;292(6):2174-2181
pubmed: 28035001
J Cell Physiol. 2008 Sep;216(3):603-14
pubmed: 18366072
Cell Host Microbe. 2015 Jul 8;18(1):86-95
pubmed: 26159721
BMC Genomics. 2015 Feb 28;16:143
pubmed: 25765891
Curr Opin Virol. 2018 Aug;31:9-16
pubmed: 30114593
PLoS Pathog. 2013;9(4):e1003312
pubmed: 23637602