title: Identification of the structural basis of thermal lability of a virus provides a rationale for improved vaccines.
abstract: Virus stability and dynamics play critical roles during infection. Some viruses, including foot-and-mouth disease virus (FMDV), are surprisingly prone to thermal dissociation outside the cell. The structural bases and functional implications of this distinctive trait were essentially unknown. This study (1) uncovers the structural determinants of FMDV thermolability, (2) investigates the relationship between virus thermolability and infectivity, and (3) provides a structure-based rationale for engineering thermostable virus particles to develop improved vaccines and nanocontainers. The results reveal that negatively charged residues close to protein-protein interfaces exert electrostatic repulsions between capsid subunits and mediate the sensitivity of the virion to thermal dissociation, even at neutral pH. Based on these results, a series of fully infectious virions of increased thermostability were engineered by individually removing different carboxylates involved in intersubunit repulsions. The implications for virus biology and the design of thermostable vaccines are discussed.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Madrid 28049, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Rincón
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Madrid 28049, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Rodríguez-Huete
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Madrid 28049, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: López-Argüello
authors.affiliation: Departamento de Química Física, Universidad de Granada, Granada 18071, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Ibarra-Molero
authors.affiliation: Departamento de Química Física, Universidad de Granada, Granada 18071, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Sanchez-Ruiz
authors.affiliation: Division Virology, Central Veterinary Institute Wageningen UR, P.O. Box 65, Lelystad 8200 AB, the Netherlands.
authors.forename: Michiel M
authors.initials: MM
authors.lastname: Harmsen
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Madrid 28049, Spain. Electronic address: mgarcia@cbm.csic.es.
authors.forename: Mauricio G
authors.initials: MG
authors.lastname: Mateu
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000502:physiology*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010641:Phenotype; D012367:RNA, Viral / Q000235:genetics*; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013696:Temperature; D014162:Transfection; D014765:Viral Vaccines / Q000737:chemistry*; D014771:Virion / Q000737:chemistry* / Q000235:genetics; D016662:Virus Integration
chemical_list: D036022:Capsid Proteins; D012367:RNA, Viral; D014765:Viral Vaccines