Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid.
Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit the pathogenic evolutionary potential of this enteric virus. In animals lacking ty...
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2021
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oai:doaj.org-article:90fb07bf8a2e40fb883cfc49c1867b662021-12-02T19:59:37ZNorovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid.1553-73661553-737410.1371/journal.ppat.1009402https://doaj.org/article/90fb07bf8a2e40fb883cfc49c1867b662021-03-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009402https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit the pathogenic evolutionary potential of this enteric virus. In animals lacking type I IFN signaling, the nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion of a single nucleotide. This nucleotide change resulted in amino acid substitution F514I in the viral capsid, which led to >10,000-fold higher replication in systemic organs including the brain. Pathogenicity was mediated by enhanced recruitment and infection of intestinal myeloid cells and increased extraintestinal dissemination of virus. Interestingly, the trade-off for this mutation was reduced fitness in an IFN-competent host, in which CR6 bearing F514I exhibited decreased intestinal replication and shedding. In an immunodeficient context, a spontaneous amino acid change can thus convert a relatively avirulent viral strain into a lethal pathogen.Forrest C WalkerEbrahim HassanStefan T PetersonRachel RodgersLawrence A SchrieferCassandra E ThompsonYuhao LiGowri KalugotlaCarla Blum-JohnstonDylan LawrenceBroc T McCuneVincent R GrazianoLarissa LushniakSanghyun LeeAlexa N RothStephanie M KarstTimothy J NiceJonathan J MinerCraig B WilenMegan T BaldridgePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 3, p e1009402 (2021) |
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DOAJ |
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DOAJ |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Forrest C Walker Ebrahim Hassan Stefan T Peterson Rachel Rodgers Lawrence A Schriefer Cassandra E Thompson Yuhao Li Gowri Kalugotla Carla Blum-Johnston Dylan Lawrence Broc T McCune Vincent R Graziano Larissa Lushniak Sanghyun Lee Alexa N Roth Stephanie M Karst Timothy J Nice Jonathan J Miner Craig B Wilen Megan T Baldridge Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid. |
| description |
Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit the pathogenic evolutionary potential of this enteric virus. In animals lacking type I IFN signaling, the nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion of a single nucleotide. This nucleotide change resulted in amino acid substitution F514I in the viral capsid, which led to >10,000-fold higher replication in systemic organs including the brain. Pathogenicity was mediated by enhanced recruitment and infection of intestinal myeloid cells and increased extraintestinal dissemination of virus. Interestingly, the trade-off for this mutation was reduced fitness in an IFN-competent host, in which CR6 bearing F514I exhibited decreased intestinal replication and shedding. In an immunodeficient context, a spontaneous amino acid change can thus convert a relatively avirulent viral strain into a lethal pathogen. |
| format |
article |
| author |
Forrest C Walker Ebrahim Hassan Stefan T Peterson Rachel Rodgers Lawrence A Schriefer Cassandra E Thompson Yuhao Li Gowri Kalugotla Carla Blum-Johnston Dylan Lawrence Broc T McCune Vincent R Graziano Larissa Lushniak Sanghyun Lee Alexa N Roth Stephanie M Karst Timothy J Nice Jonathan J Miner Craig B Wilen Megan T Baldridge |
| author_facet |
Forrest C Walker Ebrahim Hassan Stefan T Peterson Rachel Rodgers Lawrence A Schriefer Cassandra E Thompson Yuhao Li Gowri Kalugotla Carla Blum-Johnston Dylan Lawrence Broc T McCune Vincent R Graziano Larissa Lushniak Sanghyun Lee Alexa N Roth Stephanie M Karst Timothy J Nice Jonathan J Miner Craig B Wilen Megan T Baldridge |
| author_sort |
Forrest C Walker |
| title |
Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid. |
| title_short |
Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid. |
| title_full |
Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid. |
| title_fullStr |
Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid. |
| title_full_unstemmed |
Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid. |
| title_sort |
norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/90fb07bf8a2e40fb883cfc49c1867b66 |
| work_keys_str_mv |
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1718375736852611072 |