Temporal Evolutionary Dynamics of Norovirus GII.4 Variants in China between 2004 and 2015

BACKGROUND Noroviruses are one of the major causes of acute human nonbacterial gastroenteritis, and genotype II.4 (GII.4) has accounted for the majority of adult outbreaks. In addition, novel epidemic strain emerges every 2 to 3 years and spreads globally in months. There are little data reporting the evolutionary dynamics of GII.4 variants along a specific period in China. METHODS All norovirus GII.4 sequences in China were downloaded from GenBank Database. Phylogenetic tree was constructed by MEGA and Bayesian evolutionary inference techniques were applied by BEAST software to study the genetic relationships, evolution rate, evolutionary time scale and the demographic history of GII.4 variants. Homology models were predicted by SWISS-MODEL to analyze the spatial structure changes. RESULTS During the 12-year period, 624 GII.4 sequences were subtyped into six GII.4 variants (clusters). A rate of 4.74×10-3, 6.99×10-3 and 7.68×10-3 nucleotide substitutions/site/year for the strict, uncorrelated log-normal and uncorrelated exponential derivation clocks were estimated, respectively. Three amino acid mutations (G255S, S393G and H414P) in both Den Haag_2006b sub-clusters and six mutations (I244T, N309S, A377T, T244I, T377A and S393G) in three Sydney_2012 sub-clusters were observed. CONCLUSIONS The temporal distribution pattern of noroviruses GII.4 lineages in China was similar to the worldwide observation. The evolutionary rate of GII.4 was consistent with the global studies. Amino acid changes in the vicinity of norovirus epitope may have profound influences on carbohydrate binding affinity between different sub-clusters of norovirus variants. Hence understanding the evolutionary dynamics of norovirus is of great value for developing effective prevention and control strategies.