A highly structured nuclease-resistant, noncoding RNA produced by Flavoviruses is required for pathogenicity

G.P. Pijlman, A. Funk, N. Kondratieva, J.Y. Leung, L.M. van der Aa, W.J. Liu, A.C. Palmenberg, P.Y. Shi, A.A. Khromykh

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247 Citations (Scopus)

Abstract

Viral noncoding RNAs have been shown to play an important role in virus-host interplay to facilitate virus replication. We report that members of the genus Flavivirus, a large group of medically important encephalitic RNA viruses, produce a unique and highly structured noncoding RNA of 0.30.5 kb derived from the 3 untranslated region of the viral genome. Using West Nile virus as a model, we show that this subgenomic RNA is a product of incomplete degradation of viral genomic RNA by cellular ribonucleases. Highly conserved RNA structures located at the beginning of the 3 untranslated region render this RNA resistant to nucleases, and the resulting subgenomic RNA product is essential for virus-induced cytopathicity and pathogenicity. Thus, flaviviruses evolved a unique strategy to generate a noncoding RNA product that allows them to kill the host more efficiently.
Original languageEnglish
Pages (from-to)579-591
JournalCell Host & Microbe
Volume4
Issue number6
DOIs
Publication statusPublished - 2008

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Keywords

  • west-nile-virus
  • unfolded protein response
  • kunjin virus
  • secondary structure
  • encephalitis-virus
  • saccharomyces-cerevisiae
  • cyclization sequences
  • untranslated region
  • genetic algorithm
  • apoptotic pathway

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