
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2023.05.30.542907
preprint
2
Article
Intra- and Inter-host Evolution of Human Norovirus in Healthy Adults
Ramani Sasirekha http://orcid.org/0000-0001-5631-8534

Javornik Cregeen Sara J. http://orcid.org/0009-0000-2698-6478

Surathu Anil http://orcid.org/0000-0002-4780-3746

Neill Frederick H. http://orcid.org/0000-0001-7792-3135

Muzny Donna M. http://orcid.org/0000-0002-3055-0359

Doddapaneni Harsha
Menon Vipin K. http://orcid.org/0000-0001-7404-678X

Hoffman Kristi L.
Ross Matthew C.
Metcalf Ginger http://orcid.org/0000-0002-8316-0071

Opekun Antone R. http://orcid.org/0000-0003-4837-6480

Graham David Y.
Gibbs Richard A.
Petrosino Joseph F. http://orcid.org/0000-0002-4046-6898

Estes Mary K. http://orcid.org/0000-0002-4813-4249

Atmar Robert L.
05 9 2024
2023.05.30.542907https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2023.05.30.542907
nihpp-2023.05.30.542907.pdf
ABSTRACT

Background

Human noroviruses are a leading cause of acute and sporadic gastroenteritis worldwide. The evolution of human noroviruses in immunocompromised persons has been evaluated in many studies. Much less is known about the evolutionary dynamics of human norovirus in healthy adults.

Methods

We used sequential samples collected from a controlled human infection study with GI.1/Norwalk/US/68 virus to evaluate intra- and inter-host evolution of a human norovirus in healthy adults. Up to 12 samples from day 1 to day 56 post-challenge were sequenced using a norovirus-specific capture probe method.

Results

Complete genomes were assembled, even in samples that were below the limit of detection of standard RT-qPCR assays, up to 28 days post-challenge. Analysis of 123 complete genomes showed changes in the GI.1 genome in all persons, but there were no conserved changes across all persons. Single nucleotide variants resulting in non-synonymous amino acid changes were observed in all proteins, with the capsid VP1 and nonstructural protein NS3 having the largest numbers of changes.

Conclusions

These data highlight the potential of a new capture-based sequencing approach to assemble human norovirus genomes with high sensitivity and demonstrate limited conserved immune pressure-driven evolution of GI.1 virus in healthy adults.
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pmc
