Publication Date:
2014-10-21
Description:
Hepatitis A virus (HAV) remains enigmatic, despite 1.4 million cases worldwide annually. It differs radically from other picornaviruses, existing in an enveloped form and being unusually stable, both genetically and physically, but has proved difficult to study. Here we report high-resolution X-ray structures for the mature virus and the empty particle. The structures of the two particles are indistinguishable, apart from some disorder on the inside of the empty particle. The full virus contains the small viral protein VP4, whereas the empty particle harbours only the uncleaved precursor, VP0. The smooth particle surface is devoid of depressions that might correspond to receptor-binding sites. Peptide scanning data extend the previously reported VP3 antigenic site, while structure-based predictions suggest further epitopes. HAV contains no pocket factor and can withstand remarkably high temperature and low pH, and empty particles are even more robust than full particles. The virus probably uncoats via a novel mechanism, being assembled differently to other picornaviruses. It utilizes a VP2 'domain swap' characteristic of insect picorna-like viruses, and structure-based phylogenetic analysis places HAV between typical picornaviruses and the insect viruses. The enigmatic properties of HAV may reflect its position as a link between 'modern' picornaviruses and the more 'primitive' precursor insect viruses; for instance, HAV retains the ability to move from cell-to-cell by transcytosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773894/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773894/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Xiangxi -- Ren, Jingshan -- Gao, Qiang -- Hu, Zhongyu -- Sun, Yao -- Li, Xuemei -- Rowlands, David J -- Yin, Weidong -- Wang, Junzhi -- Stuart, David I -- Rao, Zihe -- Fry, Elizabeth E -- 075491/Z/04/Wellcome Trust/United Kingdom -- G1000099/Medical Research Council/United Kingdom -- England -- Nature. 2015 Jan 1;517(7532):85-8. doi: 10.1038/nature13806. Epub 2014 Oct 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China. ; Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK. ; 1] National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China [2] Sinovac Biotech Co., Ltd, Beijing 100085, China. ; National Institutes for Food and Drug Control, No. 2, TiantanXili, Beijing 100050, China. ; Institute of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. ; Sinovac Biotech Co., Ltd, Beijing 100085, China. ; 1] Division of Structural Biology, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK [2] Diamond Light Sources, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK. ; 1] National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China [2] Laboratory of Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China [3] State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25327248" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Capsid/chemistry
;
Capsid Proteins/chemistry
;
Crystallography, X-Ray
;
*Evolution, Molecular
;
Hepatitis A virus/*chemistry
;
Hot Temperature
;
Humans
;
Hydrogen-Ion Concentration
;
Insects/virology
;
Models, Molecular
;
Phylogeny
;
Picornaviridae/*chemistry
;
Transcytosis
;
Virion/chemistry
;
Virus Internalization
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
