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

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.RNA viruses, such as polioviruses, have a great evolutionary capacity and can adapt quickly during infection. Here, the authors show that poliovirus infection in mice requires adaptation to innate immune microenvironments encountered in different tissues.

SUBMITTER: Xiao Y

PROVIDER: S-EPMC5575128 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Xiao Yinghong Y Dolan Patrick Timothy PT Goldstein Elizabeth Faul EF Li Min M Farkov Mikhail M Brodsky Leonid L Andino Raul R

Nature communications 20170829 1

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 ac ...[more]

PMID: 28851882

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Project description:BACKGROUND:Maternal poliovirus antibodies could provide passive immunity to the newborns from poliovirus infection during their first few months of life, but they may impair the immune responses of infants to the poliovirus vaccine as well. In our study, we pooled the data from three clinical trials of the inactivated poliovirus vaccine (IPV) based on Sabin strains to investigate the effect of maternal poliovirus antibodies on the immune responses of infants to poliovirus vaccines. METHODS:There were five groups in the pooled analysis, including low-dose Sabin IPV, medium-dose Sabin IPV, high-dose Sabin IPV, control Sabin IPV, and control Salk IPV groups. We reclassified the infants in different groups according to their maternal poliovirus antibodies by two methods, the first one included maternal antibody negative (<?1:8) and maternal antibody positive (?1:8), and the second one included maternal antibody titer <?1:8, 1:8?~?<?1:32 and???1:32. Then, we compared the geometric mean titers (GMTs), geometric mean antibody fold increases (GMIs) and seroconversion rates of poliovirus type-specific neutralizing antibodies after vaccination among participants with different maternal poliovirus antibody levels. RESULTS:The GMTs and GMIs of three types of poliovirus antibodies after vaccination in maternal antibody negative participants were significantly higher than those in maternal antibody positive participants. The seroconversion rates of type II and type III poliovirus antibodies in maternal antibody positive participants were significantly lower than those in maternal antibody negative participants. Among participants with maternal antibody titer <?1:8, 1:8?~?<?1:32 and???1:32, the GMTs and GMIs of three types of poliovirus antibodies after vaccination showed a tendency to decline with the increasing of maternal antibody levels. The seroconversion rates of three types of poliovirus antibodies in participants with maternal antibody titer ?1:32 were significantly lower than those in participants with maternal antibody titer <?1:8 and 1:8?~?<?1:32. CONCLUSIONS:Maternal poliovirus antibodies interfered with the immune responses of infants to poliovirus vaccines, and a high level of maternal antibodies exhibited a greater dampening effect. TRIAL REGISTRATION:ClinicalTrials.gov NCT04264598 February 11, 2020; ClinicalTrials.gov NCT04264546 February 11, 2020; ClinicalTrials.gov NCT03902054 April 3, 2019. Retrospectively registered.

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

Publications

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

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