Agosto, Melina A.Myers, Kimberly S.Ivanovic, TijanaNibert, Max L.2019-10-142008Agosto, M. A., K. S. Myers, T. Ivanovic, and M. L. Nibert. 2008. “A Positive-Feedback Mechanism Promotes Reovirus Particle Conversion to the Intermediate Associated with Membrane Penetration.” Proceedings of the National Academy of Sciences 105 (30): 10571–76. doi:10.1073/pnas.0802039105.0027-84240744-28311091-6490http://nrs.harvard.edu/urn-3:HUL.InstRepos:41543010Membrane 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 mu 1N, which is released from particles during conversion, was sufficient for promoting activity. A mutant that does not undergo mu 1N 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-feed back 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.en-USJournal Article2019-10-1410.1073/pnas.0802039105