Structure and Characterization of Crimean-Congo Hemorrhagic Fever Virus GP38.
Animals
Antibodies, Viral
/ immunology
Cloning, Molecular
Crystallography, X-Ray
Disease Models, Animal
Female
Glycoproteins
/ chemistry
Hemorrhagic Fever Virus, Crimean-Congo
/ genetics
Hemorrhagic Fever, Crimean
/ immunology
Humans
Intercellular Signaling Peptides and Proteins
Mice
Mice, Knockout
Models, Molecular
Protein Conformation
STAT1 Transcription Factor
/ genetics
Sequence Analysis, Protein
X-ray crystallography
bunyavirus
nairovirus
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
31 03 2020
31 03 2020
Historique:
received:
26
11
2019
accepted:
26
01
2020
pubmed:
31
1
2020
medline:
29
9
2020
entrez:
31
1
2020
Statut:
epublish
Résumé
Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of the most widespread tick-borne viral infection in humans. CCHFV encodes a secreted glycoprotein (GP38) of unknown function that is the target of a protective antibody. Here, we present the crystal structure of GP38 at a resolution of 2.5 Å, which revealed a novel fold primarily consisting of a 3-helix bundle and a β-sandwich. Sequence alignment and homology modeling showed distant homology between GP38 and the ectodomain of Gn (a structural glycoprotein in CCHFV), suggestive of a gene duplication event. Analysis of convalescent-phase sera showed high titers of GP38 antibodies indicating immunogenicity in humans during natural CCHFV infection. The only protective antibody for CCHFV in an adult mouse model reported to date, 13G8, bound GP38 with subnanomolar affinity and protected against heterologous CCHFV challenge in a STAT1-knockout mouse model. Our data strongly suggest that GP38 should be evaluated as a vaccine antigen and that its structure provides a foundation to investigate functions of this protein in the viral life cycle.
Identifiants
pubmed: 31996434
pii: JVI.02005-19
doi: 10.1128/JVI.02005-19
pmc: PMC7108853
pii:
doi:
Substances chimiques
Antibodies, Viral
0
Glycoproteins
0
Intercellular Signaling Peptides and Proteins
0
STAT1 Transcription Factor
0
Stat1 protein, mouse
0
structural-GP protein, Bos taurus
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI132246
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142777
Pays : United States
Informations de copyright
Copyright © 2020 Mishra et al.
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