Genomic nucleotide sequence of a foot-and-mouth disease virus clone and its persistent derivatives. Implications for the evolution of viral quasispecies during a persistent infection

Virus Res. 1999 Nov;64(2):161-71. doi: 10.1016/s0168-1702(99)00089-1.

Abstract

The consensus nucleotide sequence of the entire genome of foot-and-mouth disease virus (FMDV) (biological clone C-S8c1) has been completed, and compared with that of two persistent derivatives R99 and R146, rescued after 99 and 146 passages of the carrier BHK-21 cells. Consensus sequences were determined directly from supernatants of persistently infected cells, without intervening cytolytic amplification of the viruses. These genomic sequences have also been compared with that of FMDV R100, a virus that was also rescued from persistently infected cells, but that was subjected to cytolytic amplification prior to sequencing. Mutation frequencies for R99 and R146 relative to C-S8c1 were in the range of 2.8x10(-3) to 7.7x10(-3) substitutions per nucleotide for the 5'-UTR and the L-, P1-, P2- and P3-coding regions. No mutations were fixed in the polymerase (3D)-coding region. Striking contrasts were noted regarding the distribution of mutation types along the persistent genomes, notably the complete absence of transversion mutations within the 5'-UTR, compared with 53% transversions in the L- and P1-coding regions. The sequencing results presented here, combined with previous sequences of FMDV C-S8c1 genomes at the onset of persistence, provide evidence of sequence fluctuations with a non-linear accumulation of mutations during prolonged persistence, a hallmark of quasispecies dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • Animals
  • Aphthovirus / genetics*
  • Base Sequence
  • Cell Line
  • Cricetinae
  • Evolution, Molecular
  • Genome, Viral*
  • Molecular Sequence Data
  • Point Mutation
  • RNA, Viral / analysis*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • 3' Untranslated Regions
  • 5' Untranslated Regions
  • RNA, Viral

Associated data

  • GENBANK/AJ133357
  • GENBANK/AJ133358
  • GENBANK/AJ133359