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Hepatitis A virus capsid structure

Abstract:
Hepatitis A virus (HAV) has been enigmatic, evading detailed structural analysis for many years. Its recently determined high-resolution structure revealed an angular surface without the indentations often characteristic of receptor-binding sites. The viral protein 1 (VP1) β-barrel shows no sign of a pocket factor and the amino terminus of VP2 displays a “domain swap” across the pentamer interface, as in a subset of mammalian picornaviruses and insect picorna-like viruses. Structure-based phylogeny confirms this placement. These differences suggest an uncoating mechanism distinct from that of enteroviruses. An empty capsid structure reveals internal differences in VP0 and the VP1 amino terminus connected with particle maturation. An HAV/Fab complex structure, in which the antigen-binding fragment (Fab) appears to act as a receptor–mimic, clarifies some historical epitope mapping data, but some remain difficult to reconcile. We still have little idea of the structural features of enveloped HAV particles.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1101/cshperspect.a031807

Authors

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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM
Sub department:
Human Genetics Wt Centre
Oxford college:
Hertford College
Role:
Author
ORCID:
0000-0002-3426-4210
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Structural Biology
Role:
Author
ORCID:
0000-0003-4015-1404
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM
Sub department:
Structural Biology
Role:
Author


Publisher:
Cold Spring Harbor Labaratory Press
Journal:
Cold Spring Harbor Perspectives in Medicine More from this journal
Volume:
9
Issue:
5
Article number:
a031807doi
Publication date:
2018-07-23
Acceptance date:
2018-04-12
DOI:
EISSN:
2157-1422
Pmid:
30037986


Language:
English
Pubs id:
pubs:891344
UUID:
uuid:3df4f2c8-0107-483b-b70f-7359f97e9b82
Local pid:
pubs:891344
Source identifiers:
891344
Deposit date:
2019-02-22
ARK identifier:

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