Norovirus evolution in immunodeficient mice reveals potentiated pathogenicity via a single nucleotide change in the viral capsid

• DOI: 10.1371/journal.ppat.1009402
• Publication Date: 2021-03-11T18:53:05Z
• Authors: Forrest C. Walker; Ebrahim Hassan; Stefan T. Peterson; Rachel Rodgers; Lawrence A. Schri...; Cassandra E. Thom...; 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
• Keywords: Murine norovirus

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 pathogenic evolutionary potential this enteric virus. In animals lacking type I signaling, nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion a single nucleotide. This nucleotide change resulted in amino acid substitution F514I capsid, which led >10,000-fold higher replication systemic organs including brain. Pathogenicity was mediated by recruitment infection intestinal myeloid cells increased extraintestinal dissemination Interestingly, trade-off for mutation reduced fitness an IFN-competent host, bearing exhibited decreased shedding. immunodeficient context, spontaneous can thus convert relatively avirulent into lethal pathogen.