Within-host evolution results in antigenically distinct GII.4 noroviruses

Debbink, Kari; Lindesmith, Lisa C.; Ferris, Martin T.; Swanstrom, Jesica; Beltramello, Martina; Corti, Davide; Lanzavecchia, Antonio; Baric, Ralph S.

doi:10.1128/JVI.00203-14

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Journal article

Within-host evolution results in antigenically distinct GII.4 noroviruses

Debbink, Kari Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA
Lindesmith, Lisa C. Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
Ferris, Martin T. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA
Swanstrom, Jesica Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
Beltramello, Martina Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Corti, Davide Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Humabs Biomed SA, Bellinzona, Switzerland
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute of Microbiology, ETH Zurich, Zurich, Switzerland
Baric, Ralph S. Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA - Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA

03.06.2014

Published in:

Journal of virology. - 2014, vol. 88, no. 13, p. 7244–7255

English Genogroup II, genotype 4 (GII.4) noroviruses are known to rapidly evolve, with the emergence of a new primary strain every 2 to 4 years as herd immunity to the previously circulating strain is overcome. Because viral genetic diversity is higher in chronic than in acute infection, chronically infected immunocompromised people have been hypothesized to be a potential source for new epidemic GII.4 strains. However, while some capsid protein residues are under positive selection and undergo patterned changes in sequence variation over time, the relationships between genetic variation and antigenic variation remains unknown. Based on previously published GII.4 strains from a chronically infected individual, we synthetically reconstructed virus- like particles (VLPs) representing early and late isolates from a small-bowel transplant patient chronically infected with norovirus, as well as the parental GII.4-2006b strain. We demonstrate that intrahost GII.4 evolution results in the emergence of antigenically distinct strains over time, comparable to the variation noted between the chronologically predominant GII.4 strains GII.4-2006b and GII.4-2009. Our data suggest that in some individuals the evolution that occurs during a chronic norovirus infection overlaps with changing antigenic epitopes that are associated with successive outbreak strains and may select for isolates that are potentially able to escape herd immunity from earlier isolates.

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