Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses

Yinghong Xiao, Patrick Timothy Dolan, Elizabeth Faul Goldstein, Min Li, Mikhail Farkov, Leonid Brodsky, Raul Andino

Research output: Contribution to journalArticlepeer-review


RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection. Here we show that poliovirus infection in immune-competent mice requires adaptation to tissue-specific innate immune microenvironments. The ability of the virus to establish robust infection and virulence correlates with its evolutionary capacity. We further identify a region in the multi-functional poliovirus protein 2B as a hotspot for the accumulation of minor alleles that facilitate a more effective suppression of the interferon response. We propose that population genetic dynamics enables poliovirus spread between tissues through optimization of the genetic composition of low frequency variants, which together cooperate to circumvent tissue-specific challenges. Thus, intrahost virus evolution determines pathogenesis, allowing a dynamic regulation of viral functions required to overcome barriers to infection.

Original languageEnglish
Article number375
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2017

Bibliographical note

Funding Information:
We thank Drs. Judith Frydman, Andrew Macadam and members of Andino lab for critical discussions and comments for manuscript preparation. P.T.D acknowledges support from NIH F32 Fellowship GM113483-01. This work was supported by NIH (R01, AI36178, AI40085, P01 AI091575) and the University of California (CCADD), and DoD-DARPA.

Publisher Copyright:
© 2017 The Author(s).

ASJC Scopus subject areas

  • Chemistry (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Physics and Astronomy (all)


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