title: A positive-feedback mechanism promotes reovirus particle conversion to the intermediate associated with membrane penetration.
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.
authors.affiliation: 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.
authors.forename: Melina A
authors.initials: MA
authors.lastname: Agosto
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Myers
authors.forename: Tijana
authors.initials: T
authors.lastname: Ivanovic
authors.forename: Max L
authors.initials: ML
authors.lastname: Nibert
mesh_terms: D000818:Animals; D002213:Capsid / Q000737:chemistry; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D000939:Epitopes; D004912:Erythrocytes / Q000378:metabolism; D025461:Feedback, Physiological; D006461:Hemolysis; D007313:Insecta; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D012087:Reoviridae / Q000235:genetics*; D013696:Temperature
chemical_list: D000939:Epitopes