Year-end Sale % OFF 
Abstract
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.
Highlights
RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection
Our measurements confirmed that GD displays a 3-fold lower mutation rate compared with wild type (WT) (Fig. 1b, P < 0.05, n = 7)
To examine the hypothesis that rapid viral adaptation is required to overcome in vivo selective pressures, such as innate immune responses, we compared the outcome of infection with WT and GD viruses in a murine model
Summary
RNA viruses, such as poliovirus, have a great evolutionary capacity, allowing them to quickly adapt and overcome challenges encountered during infection. RNA viruses exist as dynamic and diverse populations that rapidly adapt to selective pressures. As lineages carrying beneficial mutations arise in the population, they accumulate detrimental mutations which prevent them from being effectively selected This increasing mutational load slows the rate of evolution, an effect known as “Muller’s Ratchet”. As evidence of the strong selective pressure that innate immunity places on viral populations, viruses have evolved many mechanisms to directly counteract these signals and responses[17,18,19,20]. Limited detection level is 20 PFU per gram tissue of the virus population[1, 2, 21,22,23,24], the mechanistic links between diversity, adaptation, pathogenesis and in vivo selective pressures are not well understood. We use poliovirus as a model to examine these questions and to establish whether and how a virus’ ability to adapt facilitates viral spread and pathogenicity
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
