Synchronous loss of quasispecies memory in parallel viral lineages: a deterministic feature of viral quasispecies

J Mol Biol. 2003 Oct 24;333(3):553-63. doi: 10.1016/j.jmb.2003.08.054.

Abstract

Viral quasispecies are endowed with a memory of their past evolutionary history in the form of minority genomes of their mutant spectra. To determine the fate of memory genomes in evolving viral quasispecies, we have measured memory levels of antigenic variant of foot-and-mouth disease virus (FMDV) RED, which includes an Arg-Glu-Asp (RED) at a surface antigenic loop of the viral capsid. The RED reverted to the standard Arg-Gly-Asp (RGD), and the RED remained as memory in the evolving quasispecies. In four parallel evolutionary lineages, memory reduction followed a strikingly similar pattern, and at passage 60 memory levels were indistinguishable from those of control populations (devoid of memory). Nucleotide sequence analyses indicated that memory loss occurred synchronously despite its ultimate molecular basis being the stochastic occurrence of mutations in the evolving quasispecies. These results on the kinetics of memory levels have unveiled a deterministic feature of viral quasispecies. Molecular mechanisms that may underlie synchronous memory loss are the averaging of noise signals derived from mutational input, and constraints to genome diversification imposed by a nucleotide sequence context in the viral genome. Possible implications of the behaviour of complex, adaptive viral systems as experimental models to address primary mechanisms of neurological memory are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / immunology
  • Base Sequence
  • Capsid Proteins / chemistry
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology
  • Cell Line
  • Epitopes / genetics
  • Evolution, Molecular*
  • Foot-and-Mouth Disease Virus / chemistry
  • Foot-and-Mouth Disease Virus / genetics*
  • Foot-and-Mouth Disease Virus / immunology
  • Genetic Variation*
  • Memory
  • Models, Genetic
  • Models, Neurological
  • Mutation
  • RNA, Viral / genetics
  • Serial Passage
  • Stochastic Processes

Substances

  • Antibodies, Monoclonal
  • Capsid Proteins
  • Epitopes
  • RNA, Viral