Spatiotemporal evolutionary dynamics of norovirus GII.4 variants

Background: Noroviruses (NoVs) are the second most common cause of sporadic childhood gastroenteritis worldwide. NoVs of the GII.4 genotype are predominant globally and undergo continuous evolution in the VP1 gene, encoding the major capsid protein, resulting in the emergence of novel variants, with fourteen GII.4 variants identified to date. Methods: The present study investigated the spatiotemporal evolutionary dynamics of the globally circulating GII.4 NoVs using Bayesian approach, phylogeographic, and migration pattern analyses on a dataset of complete VP1 sequences representing each of the GII.4 variants. Results: The estimated mean evolutionary rate for GII.4 VP1 was 5.1x10-3 nucleotide substitutions per site per year (sub/site/yr), the time to Most Recent Common Ancestor (tMRCA) was ~1971, and the most probable ancestral location was the United States of America (USA). The fourteen known GII.4 variants displayed variable evolutionary rates (4.5–7.4x10-3 sub/site/yr) and tMRCA (~1984 to ~2006), with the majority having USA/Asia as their ancestral location. Migration pattern analysis indicated the important role of Australia-New Zealand, India, and Southern Europe in the global dispersal of GII.4 noroviruses. Conclusion: The study contributes to the understanding of GII.4 norovirus evolutionary dynamics.