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

Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10571-6. doi: 10.1073/pnas.0802039105. Epub 2008 Jul 24.


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.

Publication types

  • Research Support, N.I.H., Extramural

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


  • Epitopes