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Title: Structure and Uncoating of Immature Adenovirus

Abstract

Maturation via proteolytic processing is a common trait in the viral world and is often accompanied by large conformational changes and rearrangements in the capsid. The adenovirus protease has been shown to play a dual role in the viral infectious cycle: (a) in maturation, as viral assembly starts with precursors to several of the structural proteins but ends with proteolytically processed versions in the mature virion, and (b) in entry, because protease-impaired viruses have difficulties in endosome escape and uncoating. Indeed, viruses that have not undergone proteolytic processing are not infectious. We studied the three-dimensional structure of immature adenovirus particles as represented by the adenovirus type 2 thermosensitive mutant ts1 grown under non-permissive conditions and compared it with the mature capsid. Our three-dimensional electron microscopy maps at subnanometer resolution indicate that adenovirus maturation does not involve large-scale conformational changes in the capsid. Difference maps reveal the locations of unprocessed peptides pIIIa and pVI and help define their role in capsid assembly and maturation. An intriguing difference appears in the core, indicating a more compact organization and increased stability of the immature cores. We have further investigated these properties by in vitro disassembly assays. Fluorescence and electron microscopy experiments reveal differencesmore » in the stability and uncoating of immature viruses, both at the capsid and core levels, as well as disassembly intermediates not previously imaged.« less

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
NATIONAL INSTITUTE OF HEALTH
OSTI Identifier:
1040206
Report Number(s):
BNL-90613-2009-JA
Journal ID: ISSN 0022-2836; JMOBAK; 400412000; TRN: US201210%%388
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Journal Name:
Journal of Molecular Biology
Additional Journal Information:
Journal Volume: 392; Journal Issue: 2; Journal ID: ISSN 0022-2836
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ADENOVIRUS; CONFORMATIONAL CHANGES; ELECTRON MICROSCOPY; FLUORESCENCE; IN VITRO; MUTANTS; PEPTIDES; PROCESSING; PROTEINS; RESOLUTION; STABILITY; VIRUSES; adenovirus; virus maturation; virus uncoating; virus structure; three-dimensional electron microscopy

Citation Formats

Perez-Berna, A J, Mangel, W, Marabini, R, Scheres, S. H. W., Menendez-Conejero, R., Dmitriev, I P, Curiel, D T, Flint, S J, and San Martin, C. Structure and Uncoating of Immature Adenovirus. United States: N. p., 2009. Web. doi:10.1016/j.jmb.2009.06.057.
Perez-Berna, A J, Mangel, W, Marabini, R, Scheres, S. H. W., Menendez-Conejero, R., Dmitriev, I P, Curiel, D T, Flint, S J, & San Martin, C. Structure and Uncoating of Immature Adenovirus. United States. https://doi.org/10.1016/j.jmb.2009.06.057
Perez-Berna, A J, Mangel, W, Marabini, R, Scheres, S. H. W., Menendez-Conejero, R., Dmitriev, I P, Curiel, D T, Flint, S J, and San Martin, C. 2009. "Structure and Uncoating of Immature Adenovirus". United States. https://doi.org/10.1016/j.jmb.2009.06.057.
@article{osti_1040206,
title = {Structure and Uncoating of Immature Adenovirus},
author = {Perez-Berna, A J and Mangel, W and Marabini, R and Scheres, S. H. W., Menendez-Conejero, R. and Dmitriev, I P and Curiel, D T and Flint, S J and San Martin, C},
abstractNote = {Maturation via proteolytic processing is a common trait in the viral world and is often accompanied by large conformational changes and rearrangements in the capsid. The adenovirus protease has been shown to play a dual role in the viral infectious cycle: (a) in maturation, as viral assembly starts with precursors to several of the structural proteins but ends with proteolytically processed versions in the mature virion, and (b) in entry, because protease-impaired viruses have difficulties in endosome escape and uncoating. Indeed, viruses that have not undergone proteolytic processing are not infectious. We studied the three-dimensional structure of immature adenovirus particles as represented by the adenovirus type 2 thermosensitive mutant ts1 grown under non-permissive conditions and compared it with the mature capsid. Our three-dimensional electron microscopy maps at subnanometer resolution indicate that adenovirus maturation does not involve large-scale conformational changes in the capsid. Difference maps reveal the locations of unprocessed peptides pIIIa and pVI and help define their role in capsid assembly and maturation. An intriguing difference appears in the core, indicating a more compact organization and increased stability of the immature cores. We have further investigated these properties by in vitro disassembly assays. Fluorescence and electron microscopy experiments reveal differences in the stability and uncoating of immature viruses, both at the capsid and core levels, as well as disassembly intermediates not previously imaged.},
doi = {10.1016/j.jmb.2009.06.057},
url = {https://www.osti.gov/biblio/1040206}, journal = {Journal of Molecular Biology},
issn = {0022-2836},
number = 2,
volume = 392,
place = {United States},
year = {Fri Sep 18 00:00:00 EDT 2009},
month = {Fri Sep 18 00:00:00 EDT 2009}
}