title: Molecular basis for a lack of correlation between viral fitness and cell killing capacity.
abstract: The relationship between parasite fitness and virulence has been the object of experimental and theoretical studies often with conflicting conclusions. Here, we provide direct experimental evidence that viral fitness and virulence, both measured in the same biological environment provided by host cells in culture, can be two unrelated traits. A biological clone of foot-and-mouth disease virus acquired high fitness and virulence (cell killing capacity) upon large population passages in cell culture. However, subsequent plaque-to-plaque transfers resulted in profound fitness loss, but only a minimal decrease of virulence. While fitness-decreasing mutations have been mapped throughout the genome, virulence determinants-studied here with mutant and chimeric viruses-were multigenic, but concentrated on some genomic regions. Therefore, we propose a model in which viral virulence is more robust to mutation than viral fitness. As a consequence, depending on the passage regime, viral fitness and virulence can follow different evolutionary trajectories. This lack of correlation is relevant to current models of attenuation and virulence in that virus de-adaptation need not entail a decrease of virulence.
authors: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, Madrid, Spain.
authors: Mónica
authors: M
authors: Herrera
authors: Juan
authors: J
authors: García-Arriaza
authors: Nonia
authors: N
authors: Pariente
authors: Cristina
authors: C
authors: Escarmís
authors: Esteban
authors: E
authors: Domingo
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology*; D006224:Cricetinae; D005536:Foot-and-Mouth Disease / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D014644:Genetic Variation / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics*; D014779:Virus Replication
chemical_list: D014764:Viral Proteins