Abstract
Noroviruses are a major cause of viral epidemic gastroenteritis in humans worldwide. The protease (Pro) encoded in open reading frame 1 (ORF1) is an essential enzyme for proteolysis of the viral polyprotein. Although there are some reports regarding the evolutionary analysis of norovirus GII-encoding genes, there are few reports focused on the Pro region. We analyzed the molecular evolution of the Pro region of norovirus GII using bioinformatics approaches. A time-scaled phylogenetic tree of the Pro region constructed using a Bayesian Markov chain Monte Carlo method indicated that the common ancestor of GII diverged from GIV around 1680 CE [95% highest posterior density (HPD), 1607–1749]. The GII Pro region emerged around 1752 CE (95%HPD, 1707–1794), forming three further lineages. The evolutionary rate of GII Pro region was estimated at more than 10–3 substitutions/site/year. The distribution of the phylogenetic distances of each genotype differed, and showed genetic diversity. Mapping of the negative selection and substitution sites of the Pro structure showed that the substitution sites in the Pro protein were mostly produced under neutral selection in positions structurally adjacent to the active sites for proteolysis, whereas negative selection was observed in residues distant from the active sites. The phylodynamics of GII.P4, GII.P7, GII.P16, GII.P21, and GII.P31 indicated that their effective population sizes increased during the period from 2005 to 2016 and the increase in population size was almost consistent with the collection year of these genotypes. These results suggest that the Pro region of the norovirus GII evolved rapidly, but under no positive selection, with a high genetic divergence, similar to that of the RNA-dependent RNA polymerase (RdRp) region and the VP1 region of noroviruses.
Highlights
Noroviruses (NoVs) are a major cause of acute epidemic viral gastroenteritis worldwide (Green, 2013; Robilotti et al, 2015)
The phylogenetic tree indicated that GI diverged from the common ancestor of GII, GIII, and GIV in 1143 CE (95%highest posterior density (HPD), 895–1370), and GIII diverged from the common ancestor of GII and GIV in 1250 CE (95%HPD, 1031–1447)
This study showed that the evolutionary rate of the GII Pro region was estimated at 3.94 × 10−3 substitutions/site/year, and that evolution at different rates occurred between the open reading frame 1 (ORF1) genotypes (Figure 2)
Summary
Noroviruses (NoVs) are a major cause of acute epidemic viral gastroenteritis worldwide (Green, 2013; Robilotti et al, 2015). 200,000 deaths in children less than 5 years of age are estimated to be caused by NoV infections (Patel et al, 2008). NoV belongs to the family Caliciviridae, genus Norovirus, and is classified into 10 genogroups (GI-GX) (Chhabra et al, 2019). The GI, GII, GIV, GVIII and GIX genogroups of NoV can infect humans (Chhabra et al, 2019). Previous molecular epidemiological studies have shown that some NoV GII genotypes, including GII., GII., GII., GII., and GII. are prevalent in different countries (Matsushima et al, 2015; Bruggink et al, 2016, 2018; Cannon et al, 2017; Wangchuk et al, 2017)
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