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PMID: 18653761 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

A positive-feedback mechanism promotes reovirus particle conversion to the intermediate associated with membrane penetration.

Agosto MA, Myers KS, Ivanovic T, Nibert ML

Abstract

Membrane penetration by reovirus is associated with conversion of a metastable intermediate, the ISVP, to a further-disassembled particle, the ISVP*. Factors that promote this conversion in cells are poorly understood. Here, we report the in vitro characterization of a positive-feedback mechanism for promoting ISVP* conversion. At high particle concentration, conversion approximated second-order kinetics, and products of the reaction operated in trans to promote the conversion of target ISVPs. Pore-forming peptide mu1N, which is released from particles during conversion, was sufficient for promoting activity. A mutant that does not undergo mu1N release failed to exhibit second-order conversion kinetics and also failed to promote conversion of wild-type target ISVPs. Susceptibility of target ISVPs to promotion in trans was temperature dependent and correlated with target stability, suggesting that capsid dynamics are required to expose the interacting epitope. A positive-feedback mechanism of promoting escape from the metastable intermediate has not been reported for other viruses but represents a generalizable device for sensing a confined volume, such as that encountered during cell entry.

MeSH Terms
Animals Capsid/chemistry Cattle Cell Line Cell Membrane/metabolism Epitopes Erythrocytes/metabolism Feedback, Physiological Hemolysis Insecta Kinetics Mice Models, Biological Reoviridae/genetics Temperature
Chemicals
Epitopes
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Agosto Melina A
Department of Microbiology and Molecular Genetics, Harvard Medical School, and Training Programs in Biological and Biomedical Sciences and Virology, Division of Medical Sciences, Harvard University, Boston, MA 02115, USA.
Myers Kimberly S
Ivanovic Tijana
Nibert Max L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
Published
2008-07-29
Epub
2008-00-24
Pages
10571-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2492467
Subset
IM
Grants
NIAID NIH HHS · F31 AI064142 · United States
NIAID NIH HHS · R01 AI046440 · United States
NIAID NIH HHS · R01 AI46440 · United States
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