Bottleneck-mediated quasispecies restriction during spread of an RNA virus from inoculation site to brain

Julie K. Pfeiffer, Karla Kirkegaard

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

The amplification of RNA viruses such as poliovirus is associated with high error rates, and the resulting diversity likely facilitates viral survival within an infected host. However, within individual tissues of infected hosts, there may be barriers to viral spread that limit genome sampling. We tested whether poliovirus population diversity was maintained during viral spread to the brain of poliovirus receptor-expressing mice. Each of four restriction enzyme site-tagged viruses was shown to be able to replicate in the mouse brain. However, when infection was initiated by i.m., i.v., or i.p. routes, only a subset of the members of the injected pool was detectable in the brain. This jackpot effect was the result of a bottleneck in viral transit from the inoculation site to the brain. The bottleneck was difficult to overcome, requiring a 107 increase in viral inoculum to allow representation of all or most members of the infecting pool. Therefore, the bottleneck is not likely to be a physical barrier but an antiviral state induced by a founder virus. We suggest that the innate immune response can limit viral pathogenicity by limiting the number and therefore the diversity of viruses during spread to vulnerable tissues.

Original languageEnglish (US)
Pages (from-to)5520-5525
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number14
DOIs
StatePublished - Apr 4 2006

Keywords

  • Innate immunity
  • Neurovirulence
  • Pathogenesis
  • Population genetics
  • Virus transmission

ASJC Scopus subject areas

  • General

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