Ruis, C;
Lindesmith, LC;
Mallory, ML;
Brewer-Jensen, PD;
Bryant, JM;
Costantini, V;
Monit, C;
... Breuer, J; + view all
(2020)
Preadaptation of pandemic GII.4 noroviruses in unsampled virus reservoirs years before emergence.
Virus Evol
10.1093/ve/veaa067.
(In press).
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Abstract
The control of re-occurring pandemic pathogens requires understanding the origins of new pandemic variants and the factors that drive their global spread. This is especially important for GII.4 norovirus, where vaccines under development offer promise to prevent hundreds of millions of annual gastroenteritis cases. Previous studies have hypothesized that new GII.4 pandemic viruses arise when previously circulating pandemic or pre-pandemic variants undergo substitutions in antigenic regions that enable evasion of host population immunity, as described by conventional models of antigenic drift. In contrast, we show here that the acquisition of new genetic and antigenic characteristics cannot be the proximal driver of new pandemics. Pandemic GII.4 viruses diversify and spread over wide geographical areas over several years prior to simultaneous pandemic emergence of multiple lineages, indicating that the necessary sequence changes must have occurred before diversification, years prior to pandemic emergence. We confirm this result through serological assays of reconstructed ancestral virus capsids, demonstrating that by 2003, the ancestral 2012 pandemic strain had already acquired the antigenic characteristics that allowed it to evade prevailing population immunity against the previous 2009 pandemic variant. These results provide strong evidence that viral genetic changes are necessary but not sufficient for GII.4 pandemic spread. Instead, we suggest that it is changes in host population immunity that enable pandemic spread of an antigenically preadapted GII.4 variant. These results indicate that predicting future GII.4 pandemic variants will require surveillance of currently unsampled reservoir populations. Furthermore, a broadly acting GII.4 vaccine will be critical to prevent future pandemics.
| Type: | Article |
|---|---|
| Title: | Preadaptation of pandemic GII.4 noroviruses in unsampled virus reservoirs years before emergence |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/ve/veaa067 |
| Language: | English |
| Additional information: | This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | antigenic change, phylodynamics, phylogenetics, serology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10112087 |
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