Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses: Implications for virus evolution and host persistence

P Simmonds*, A Tuplin, DJ Evans

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

169 Citations (Scopus)

Abstract

Discrete RNA secondary and higher-order structures, typically local in extent, play a fundamental role in RNA virus replication. Using new bioinformatics analysis methods, we have identified genome-scale ordered RNA structure (GORS) in many genera and families of positive-strand animal and plant RNA viruses. There was remarkably variability between genera that possess this characteristic; for example, hepaciviruses in the family Flaviviridae show evidence for extensive internal base-pairing throughout their coding sequences that was absent in both the related pestivirus and flavivirus genera. Similar genus-associated variability was observed in the Picornaviridae, the Caliciviridae, and many plant virus families. The similarity in replication strategies between genera in each of these families rules out a role for GORS in a fundamentally conserved aspect of this aspect of the virus life cycle. However, in the Picornaviridae, Flaviviridae, and Caliciviridae, the existence of GORS correlated strongly with the ability of each genus to persist in their natural hosts. This raises the intriguing possibility of a role for GORS in the modulation of innate intracellular defense mechanisms (and secondarily, the acquired immune system) triggered by double-stranded RNA, analogous in function to the expression of structured RNA transcripts by large DNA viruses. irrespective of function, the observed evolutionary conservation of GORS in many viruses imposes a considerable constraint on genome plasticity and the consequent narrowing of sequence space in which neutral drift can occur. These findings potentially reconcile the rapid evolution of RNA viruses over short periods with the documented examples of extreme conservatism evident from their intimate coevolution with their hosts.

Original languageEnglish
Pages (from-to)1337-1351
Number of pages15
JournalRNA
Volume10
Issue number9
DOIs
Publication statusPublished - Sept 2004

Keywords

  • virus
  • persistence
  • evolution
  • innate immune response
  • molecular clock
  • RNA structure
  • HEPATITIS-C VIRUS
  • ACTING REPLICATION ELEMENT
  • RIBOSOME ENTRY SITE
  • PROTEIN-KINASE PKR
  • SECONDARY STRUCTURE
  • PICORNAVIRUS RNA
  • CODING REGION
  • INTERFERON
  • PREDICTION
  • IDENTIFICATION

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