Structural basis for the interaction of human herpesvirus 6B tetrameric glycoprotein complex with the cellular receptor, human CD134.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
03
02
2020
accepted:
20
05
2020
entrez:
18
7
2020
pubmed:
18
7
2020
medline:
25
8
2020
Statut:
epublish
Résumé
A unique glycoprotein is expressed on the virus envelope of human herpesvirus 6B (HHV-6B): the complex gH/gL/gQ1/gQ2 (hereafter referred to as the HHV-6B tetramer). This tetramer recognizes a host receptor expressed on activated T cells: human CD134 (hCD134). This interaction is essential for HHV-6B entry into the susceptible cells and is a determinant for HHV-6B cell tropism. The structural mechanisms underlying this unique interaction were unknown. Herein we solved the interactions between the HHV-6B tetramer and the receptor by using their neutralizing antibodies in molecular and structural analyses. A surface plasmon resonance analysis revealed fast dissociation/association between the tetramer and hCD134, although the affinity was high (KD = 18 nM) and comparable to those for the neutralizing antibodies (anti-gQ1: 17 nM, anti-gH: 2.7 nM). A competition assay demonstrated that the anti-gQ1 antibody competed with hCD134 in the HHV-6B tetramer binding whereas the anti-gH antibody did not, indicating the direct interaction of gQ1 and hCD134. A single-particle analysis by negative-staining electron microscopy revealed the tetramer's elongated shape with a gH/gL part and extra density corresponding to gQ1/gQ2. The anti-gQ1 antibody bound to the tip of the extra density, and anti-gH antibody bound to the putative gH/gL part. These results highlight the interaction of gQ1/gQ2 in the HHV-6B tetramer with hCD134, and they demonstrate common features among viral ligands of the betaherpesvirus subfamily from a macroscopic viewpoint.
Identifiants
pubmed: 32678833
doi: 10.1371/journal.ppat.1008648
pii: PPATHOGENS-D-20-00217
pmc: PMC7367449
doi:
Substances chimiques
Receptors, OX40
0
TNFRSF4 protein, human
0
Viral Envelope Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008648Déclaration de conflit d'intérêts
The authors declare no conflicts.
Références
Nat Struct Mol Biol. 2010 Jul;17(7):882-8
pubmed: 20601960
Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22641-6
pubmed: 21149717
Proc Natl Acad Sci U S A. 2013 May 28;110(22):9096-9
pubmed: 23674671
J Virol. 2011 Nov;85(21):11121-30
pubmed: 21849437
J Struct Biol. 2016 Jul;195(1):93-9
pubmed: 27108186
Proc Natl Acad Sci U S A. 2015 May 12;112(19):6056-61
pubmed: 25918416
J Virol. 2002 Jul;76(13):6750-61
pubmed: 12050388
J Virol. 2004 May;78(9):4609-16
pubmed: 15078943
J Virol. 2019 May 1;93(10):
pubmed: 30842329
J Virol. 2003 Feb;77(4):2452-8
pubmed: 12551983
J Clin Microbiol. 1989 Apr;27(4):651-3
pubmed: 2542358
Lancet. 1988 May 14;1(8594):1065-7
pubmed: 2896909
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
J Virol. 2017 Mar 13;91(7):
pubmed: 28077654
J Struct Biol. 2016 Jan;193(1):1-12
pubmed: 26592709
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
J Virol. 2015 Oct;89(19):10125-9
pubmed: 26202244
Clin Infect Dis. 2013 Sep;57(5):671-81
pubmed: 23723198
Gene. 1991 Dec 15;108(2):193-9
pubmed: 1660837
Cell Microbiol. 2009 Jul;11(7):1001-6
pubmed: 19290911
PLoS Pathog. 2014 Aug 21;10(8):e1004309
pubmed: 25144748
Curr Opin Virol. 2017 Jun;24:97-104
pubmed: 28538165
Adv Exp Med Biol. 2018;1045:227-249
pubmed: 29896670
J Virol. 2004 Aug;78(15):7969-83
pubmed: 15254169
J Neurovirol. 2017 Feb;23(1):1-19
pubmed: 27538995
J Virol. 2015 May;89(9):5159-63
pubmed: 25694589
Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8703-E8710
pubmed: 28939750
Virology. 1990 Jun;176(2):625-8
pubmed: 2161152
Curr Opin Virol. 2016 Jun;18:1-8
pubmed: 26849495
Nat Microbiol. 2016 Jun 06;1(8):16082
pubmed: 27573107
Bone Marrow Transplant. 2015 Aug;50(8):1030-6
pubmed: 25915811
Sci Immunol. 2017 Jun 30;2(12):
pubmed: 28783665
J Virol. 2011 Dec;85(24):12962-71
pubmed: 21957287
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Arch Virol. 2014 May;159(5):863-70
pubmed: 24193951
Biol Blood Marrow Transplant. 2012 Nov;18(11):1638-48
pubmed: 22564265
Cell. 2018 Aug 23;174(5):1158-1171.e19
pubmed: 30057110
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):352-67
pubmed: 22505256
J Struct Funct Genomics. 2006 Mar;7(1):15-22
pubmed: 16645781
Cell. 1999 Dec 23;99(7):817-27
pubmed: 10619434
Structure. 2006 Aug;14(8):1321-30
pubmed: 16905106
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Nucleic Acids Res. 2018 Jul 2;46(W1):W296-W303
pubmed: 29788355
N Engl J Med. 1994 Aug 18;331(7):432-8
pubmed: 8035839
J Virol. 2014 Sep;88(18):10875-82
pubmed: 25008928
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
J Exp Med. 2004 Feb 16;199(4):525-33
pubmed: 14970179
Nat Commun. 2016 Dec 08;7:13557
pubmed: 27929061
Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1767-72
pubmed: 25624487
J Gen Virol. 1997 Sep;78 ( Pt 9):2171-8
pubmed: 9292004
J Struct Biol. 2012 Dec;180(3):519-30
pubmed: 23000701