Molecular Evolution of the VP1 Gene in Human Norovirus GII.4 Variants in 1974–2015

Abstract

Human norovirus (HuNoV) is a leading cause of viral gastroenteritis worldwide, of which GII.4 is the most predominant genotype. Unlike other genotypes, GII.4 has created various variants that escaped from previously acquired immunity of the host and caused repeated epidemics. However, the molecular evolutionary differences among all GII.4 variants, including recently discovered strains, have not been elucidated. Thus, we conducted a series of bioinformatic analyses using numerous, globally collected, full-length GII.4 major capsid (VP1) gene sequences (466 strains) to compare the evolutionary patterns among GII.4 variants. The time-scaled phylogenetic tree constructed using the Bayesian Markov chain Monte Carlo (MCMC) method showed that the common ancestor of the GII.4 VP1 gene diverged from GII.20 in 1840. The GII.4 genotype emerged in 1932, and then formed seven clusters including 14 known variants after 1980. The evolutionary rate of GII.4 strains was estimated to be 7.68 × 10−3 substitutions/site/year. The evolutionary rates probably differed among variants as well as domains [protruding 1 (P1), shell, and P2 domains]. The Osaka 2007 variant strains probably contained more nucleotide substitutions than any other variant. Few conformational epitopes were located in the shell and P1 domains, although most were contained in the P2 domain, which, as previously established, is associated with attachment to host factors and antigenicity. We found that positive selection sites for the whole GII.4 genotype existed in the shell and P1 domains, while Den Haag 2006b, New Orleans 2009, and Sydney 2012 variants were under positive selection in the P2 domain. Amino acid substitutions overlapped with putative epitopes or were located around the epitopes in the P2 domain. The effective population sizes of the present strains increased stepwise for Den Haag 2006b, New Orleans 2009, and Sydney 2012 variants. These results suggest that HuNoV GII.4 rapidly evolved in a few decades, created various variants, and altered its evolutionary rate and antigenicity.

Molecular Evolution of the Fusion Protein (F) Gene in Human Respirovirus 3

“…Moreover, Košutić-Gulija et al (2017) and Tsutsui et al (2017) performed a molecular epidemiologic study by the ML method using the full-length nucleotide sequences of the F gene from domestic HRV3 strains (Japanese and Croatian strains, respectively). Assessment of viral gene evolutionary rates may help to predict the emergence of new mutants adept at evading host immunity (Motoya et al, 2017). Thus, we performed time-scaled phylogenetic analysis using fulllength nucleotide sequences of hundreds of strains collected from various countries and evaluated the dominant type by cluster classification, calculating the evolutionary rates of strains belonging to each cluster and subcluster.…”

Norovirus Replication in Human Intestinal Epithelial Cells Is Restricted by the Interferon-Induced JAK/STAT Signaling Pathway and RNA Polymerase II-Mediated Transcriptional Responses

“…HuNoVs belong to one of three norovirus genogroups (GI, GII, and GIV), which are further divided into Ͼ25 genetic clusters or genotypes (6)(7)(8). Epidemiological studies have revealed that over 75% of confirmed human norovirus infections are associated with HuNoV GII (9,10). While norovirus gastroenteritis typically results in an acute and self-limiting disease, the socioeconomic impact in both developed and developing countries is estimated to be more than $60.3 billion per annum (11).…”

Norovirus GII.P16/GII.2 Strain in Shenzhen, China: A Retrospective Study

“…GII.4 Sydney2012 was only account for 3.4%. In 2016, NoV outbreaks were associated with GII.P16/GII.2 strains were reported in multiple regions in China [39,40]. In this study, we identi ed the GII.2 strain were NoV GII.P16/GII.2, and was recombinant strain as other regions in China [39,40].…”

“…In 2016, NoV outbreaks were associated with GII.P16/GII.2 strains were reported in multiple regions in China [39,40]. In this study, we identi ed the GII.2 strain were NoV GII.P16/GII.2, and was recombinant strain as other regions in China [39,40]. This study found the rst outbreak identi ed as GII.P16/GII.2 recombinant strain was September 30, 2016 in Shenzhen and then the GII.P16/GII.2 strain caused steep rise in acute gastroenteritis in Shenshen in the following months.…”