Abstract
BackgroundNoroviruses 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.MethodsAll 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.ResultsDuring 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.ConclusionsThe 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.
Highlights
Norovirus (NoV) is the most common causative agent of acute nonbacterial gastroenteritis in all ages, and almost 267 million NoV infections and over 200,000 deaths, mostly in infants and the elderly, have been identified yearly worldwide[1,2]
There are little data reporting the evolutionary dynamics of GII.4 variants along a specific period in China
Phylogenetic tree was constructed by Molecular Evolutionary Genetics Analysis (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
Summary
Norovirus (NoV) is the most common causative agent of acute nonbacterial gastroenteritis in all ages, and almost 267 million NoV infections and over 200,000 deaths, mostly in infants and the elderly, have been identified yearly worldwide[1,2]. Multiple NoV genotypes have been found cocirculating in human populations in which the GII genotype 4 (GII.4) has been the predominant genotype that cause over 80% of all NoV infections [3,4] It is the major circulating genotype in community and health-care settings with periodic emergence of novel GII. variants every 2–3 years with a total of six major GII.. There are little data reporting the evolutionary dynamics of GII. variants along a specific period in China
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