title: Thermostability of reovirus disassembly intermediates (ISVPs) correlates with genetic, biochemical, and thermodynamic properties of major surface protein mu1.
abstract: Kinetic analyses of infectivity loss during thermal inactivation of reovirus particles revealed substantial differences between virions and infectious subvirion particles (ISVPs), as well as between the ISVPs of reoviruses type 1 Lang (T1L) and type 3 Dearing (T3D). The difference in thermal inactivation of T1L and T3D ISVPs was attributed to the major surface protein mu1 by genetic analyses with reassortant viruses and recoated cores. Irreversible conformational changes in ISVP-bound mu1 were shown to accompany thermal inactivation. The thermal inactivation of ISVPs approximated first-order kinetics over a range of temperatures, permitting the use of Arrhenius plots to estimate activation enthalpies and entropies that account for the different behaviors of T1L and T3D. An effect similar to enthalpy-entropy compensation was additionally noted for the ISVPs of these two isolates. Kinetic analyses with other ISVP-like particles, including ISVPs of a previously reported thermostable mutant, provided further insights into the role of mu1 as a determinant of thermostability. Intact virions, which contain final sigma3 bound to mu1 as their major surface proteins, exhibited greater thermostability than ISVPs and underwent thermal inactivation with kinetics that deviated from first order, suggesting a role for final sigma3 in both these properties. The distinct inactivation behaviors of ISVPs are consistent with their role as an essential intermediate in reovirus entry.
authors.affiliation: Department of Chemical Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Middleton
authors.forename: Tonya F
authors.initials: TF
authors.lastname: Severson
authors.forename: Kartik
authors.initials: K
authors.lastname: Chandran
authors.forename: Anne Lynn
authors.initials: AL
authors.lastname: Gillian
authors.forename: John
authors.initials: J
authors.lastname: Yin
authors.forename: Max L
authors.initials: ML
authors.lastname: Nibert
mesh_terms: D000818:Animals; D002213:Capsid / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D036022:Capsid Proteins; D002460:Cell Line; D024882:Drug Resistance, Viral; D000431:Ethanol / Q000494:pharmacology; D006361:Heating; D006801:Humans; D007700:Kinetics; D007739:L Cells; D012089:Mammalian orthoreovirus 3 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008432:Mathematical Computing; D051379:Mice; D009036:Moths / Q000166:cytology; D016296:Mutagenesis; D030102:Orthoreovirus, Mammalian / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016601:RNA-Binding Proteins; D018411:Spodoptera / Q000166:cytology; D014758:Viral Core Proteins / Q000378:metabolism; D014771:Virion; D014775:Virus Activation
chemical_list: D036022:Capsid Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; C055356:mu1 protein, Reovirus; C053179:sigma protein 3, Reovirus; D000431:Ethanol