Mutations in West Nile virus nonstructural proteins that facilitate replicon persistence in vitro attenuate virus replication in vitro and in vivo

Shannan Rossi, Rafik Fayzulin, Nathan Dewsbury, Nigel Bourne, Peter W. Mason

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

West Nile virus (WNV) infections in vertebrates are generally acute but persistent infections have been observed. To investigate the ability of WNV to produce persistent infections, we forced subgenomic WNV replicons to replicate within a cell without causing cell death. Detailed analyses of these cell-adapted genomes revealed mutations within the nonstructural protein genes NS2A (D73H, M108K), NS3 (117Kins), NS4B (E249G) and NS5 (P528H). WNV replicons and WNVs harboring a subset of NS2A or NS3 mutations showed a reduction in genome replication, a reduction in antigen accumulation, a decrease in cytopathic effect, an increased ability to persist in cell culture and/or attenuation in vivo. Taken together, these data indicate that WNV with a defect in replication and an increased potential to persist within the host cell can be generated by point mutations at multiple independent loci, suggesting that persistent viruses could arise in nature.

Original languageEnglish (US)
Pages (from-to)184-195
Number of pages12
JournalVirology
Volume364
Issue number1
DOIs
StatePublished - Jul 20 2007

Fingerprint

West Nile virus
Replicon
Virus Replication
Mutation
Proteins
Genome
Virus Diseases
Infection
Point Mutation
Vertebrates
Cell Death
Cell Culture Techniques
In Vitro Techniques
Viruses
Antigens

Keywords

  • Attenuation
  • Flavivirus
  • Innate immune response
  • Interferon
  • Nonstructural gene
  • Persistence
  • Replication
  • Replicon
  • West Nile virus

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Mutations in West Nile virus nonstructural proteins that facilitate replicon persistence in vitro attenuate virus replication in vitro and in vivo. / Rossi, Shannan; Fayzulin, Rafik; Dewsbury, Nathan; Bourne, Nigel; Mason, Peter W.

In: Virology, Vol. 364, No. 1, 20.07.2007, p. 184-195.

Research output: Contribution to journalArticle

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