key: cord-0073218-ayxwcaib
authors: Zhu, Xi; He, Yaqing; Wei, Xingyan; Kong, Xiangyu; Zhang, Qing; Li, Jingxin; Jin, Miao; Duan, Zhaojun
title: Molecular Epidemiological Characteristics of Gastroenteritis Outbreaks Caused by Norovirus GII.4 Sydney [P31] Strains — China, October 2016–December 2020
date: 2021-12-31
journal: China CDC Wkly
DOI: 10.46234/ccdcw2021.276
sha: 6bc07d23896dfc7e8d8f7e89ccfbc6c2e4009b02
doc_id: 73218
cord_uid: ayxwcaib

INTRODUCTION: Human noroviruses are the leading cause of acute viral gastroenteritis (AGE) worldwide in all age groups. GII.4 strains have been the predominant genotype circulating globally over the last 2 decades and since 2012. GII.4 Sydney viruses have emerged and caused the majority of AGE outbreaks worldwide. METHODS: Data from norovirus outbreaks from the laboratory-based surveillance of norovirus outbreaks in China (CaliciNet China) between October 2016–December 2020 were analyzed. RESULTS: During October 2016–December 2020, 1,954 norovirus outbreaks were reported, and positive fecal samples from 1,352 (69.19%) outbreaks were genotyped. GII.4 Sydney [P31] viruses accounted for 2.1% (October 2016–August 2017), 5.5% (September 2017–August 2018), 3.3% (September 2018–August 2018), 26.6% (September 2019–August 2020), and and 1.1% (September 2020–December 2020) of GII outbreaks, respectively. Compared to reference strains of GII.4 Sydney [P31] from 2012 to 2013, 7 amino acid mutations in epitopes[A (297, 372 and 373), B (333), E (414), and H (309 and 310)] and 1 in human histo-blood group antigens binding site at site II 372 were found by analyzing 9 GII.4 Sydney [P31] complete genomic sequences. CONCLUSIONS: This report identified the genomic variation of GII.4 Sydney [P31] from CaliciNet China. Continued surveillance with prompt genotyping and genetic analysis is necessary to monitor the emergence of novel GII.4 variants.

mutations that make NoVs evade the host immune response but also by recombination at the junction of the open reading frame (ORF) 1 and 2 that can result in the emergence of a novel strain (3) .

Among the more than 30 genotypes of norovirus that cause disease in humans, GII.4 viruses have been reported to cause the majority of norovirus infections worldwide (4) . Novel GII.4 variants have emerged every several years, displacing previous dominant strains to cause a new wave of outbreaks (4) . The GII. has been continuously detected in outbreak surveillance (7) (8) . This study described the outbreaks in China caused by GII.4 Sydney [P31] from October 2016 to December 2020, as well as the genome information of GII.4 Sydney [P31], the important amino acid mutation sites of antigen epitopes and receptor binding sites, human histo-blood group antigens (HBGAs), which were assumed to be associated with the epidemic pattern of GII.4 noroviruses.

Since 2016, laboratory-based surveillance of norovirus outbreaks in China (CaliciNet China) has been conducted, which is a network of county-level, city-level, and provincial CDCs coordinated by China CDC. As a representative member of the Caliciviridae family, norovirus has cup-shaped depressions under the electron microscope, which is the origin of the network name. A detailed description of CaliciNet China has been reported previously (8) . By 2018, the number of network laboratories has increased to 31, 14 

Since CaliciNet China was launched in October 2016 in China, more laboratories were included to report norovirus outbreaks data and sequence information. Therefore, prompt analysis of the genetic characteristics and variation of norovirus strains from China was available. Moreover, the real-time monitoring of the emergence of new norovirus variants has strengthened the capacity on early warning and prediction of norovirus outbreaks in China. Our study showed the epidemiological characters of outbreaks by noroviruses and identified GII. 4 5 6 7 8 9101112 1 2 3 4 5 6 7 8 9101112 1 2 3 4 5 6 7 8 9 101112 1 2 3 4 5 6 7 8 such as Japan and the Republic of Korea, schools and kindergartens were also identified as the most common places of norovirus outbreaks in China (10-11). The high proportion of norovirus outbreaks in kindergartens and schools may be related to the high population density in these environments, as well as our enhanced monitoring and reporting of school outbreaks in China (12) .

Since mid-1995, the genotype causing the global outbreak of norovirus has only been related to the GII.4 genotype (4). Since 2012, the GII.4 Sydney variant has been predominant all over the world. Therefore, the monitoring of GII.4 Sydney strain is important for potentially emerging GII.4 variants (5). This study described the epidemiological characteristic and the genome variation of GII.4 Sydney [P31]. It was consistent that GII.4 viruses have been associated with person-to-person transmission both from this study and other previous data from CaliciNet USA and NoroNet. The GII.4 Sydney [P31] outbreaks in our study mainly occurred in childcare centers and primary schools. In other parts of the world, GII.4 Sydney viruses have been reported as the dominant genotype among adults and the elderly especially in outbreaks in long-term care facilities (13) .

Much evidence from our study suggested that GII. 

. These residue changes were likely to enable the norovirus to escape the pressure of population immunity and cause a global epidemic of norovirus once again. In addition to antigenic drift, recombination resulting in polymerase switching was also an important mechanism for the evolution of noroviruses (3) . Acquisition of the GII.P16 polymerase and/or associated nonstructural proteins appeared to be the impetus for the predominance of GII.P16-GII.4 Sydney viruses in 2015 to 2016 in the USA (5).

However, a limited number of studies have evaluated the evolutionary rate of the ORF1 gene. Each genotype has an evolutionary mechanism. Evolutionary analyses may vary depending on the genotype and the database used (15) . Future studies are needed to determine what structural differences contemporary GII.P16 polymerases have gained and what the functional role of these changes is.

There were several limitations in this study. First, local CDCs participated in the network voluntarily, so these data may only represent places covered by GII. 4 Sydney strain  Major components of the HBGA binding sites  Site I  Site II  Site III  338  339  340  341  342  343  344  345  346  347  348  349  370  371  372  373  374  375  376  440  441  442  443  444  445  446 JX459908. Note: Residues mapping on previously characterized A-H epitopes. Amino acid residues that differ from those of the prototype were highlighted in blue. Sequences of this study were in bold. Abbreviations: HBGA=histo-blood group antigen.

G C S G Y P N MH218616.1_UK_2014 T R T D G S T R G H K A D T N H D F E G C S G Y P N MK934772_CHN_2015 T R T D G S T R G H K A D T N N D F E G C S G Y P N KY407103_CHN_2016 T R T D G S T R G H K A D T N N D F E G C S G Y P N KY679162_HK_2017 T R T D G S T R G H K A D T N N D F E G C S G Y P N MN897754.1_US_2018 T R T D G S T R G H K A D T N N D F E G C S G Y P N 19GZ25205(2019) T R T D G S T R G H K A D T N N D F E G C S G Y P N 20HN059(2020.8) T R T D G S T R G H K A D T N H D F E G C S G Y P N 20HN061(2020.8) T R T D G S T R G H K A D T N H D F E G C S G Y P N 20CQ154(2020.10) T R T D G S T R G H K A D T N N D F E G C S G Y P N 20CQ185(2020.10) T R T D G S T R G H K A D T N N D F E G C S G Y P N 20HN253(2020.12) T R T D G S T R G H K A D T N N D F E G C S G Y P N 20HN255(2020.12) T R T D G S T R G H K A D T N N D F E G C S G Y P N 20HN256(2020.12) T R T D G S T R G H K A D T N N D F E G C S G Y P N 20HN261(2020.12) T R T D G S T R G H K A D T N N D F E G C S G Y P N

Calicinet China and are not generalizable. Still, China CDC is constantly making efforts to include more laboratories and build a more comprehensive surveillance system. Second, the epidemiological information collected in each outbreak was not sufficient, hindering further analysis. Third, the timeliness of the data reporting in CaliciNet China needs to be improved. Due to the increasing burden of laboratory testing caused by COVID-19, not all network members could submit data to China CDC on a monthly basis. In the future, a web-based information submission system will contribute to the near real-time surveillance network.

In conclusion, the molecular epidemiological characteristics of norovirus outbreaks and the genome variation of GII. 

The vast and 1. varied global burden of norovirus: prospects for prevention and control

The epidemiologic and clinical importance of norovirus infection

Evidence for recombination between pandemic GII.4 norovirus strains New Orleans 2009 and Sydney

Norovirus GII.4 strain antigenic variation

Genetic and epidemiologic trends of norovirus outbreaks in the United States from 2013 to 2016 demonstrated emergence of novel GII.4 recombinant viruses

Gastroenteritis outbreaks associated with the emergence of the new GII.4 Sydney norovirus variant during the epidemic of 2012/13 in Shenzhen city

Characterization of the new GII.17 norovirus variant that emerged recently as the predominant strain in China

Norovirus outbreak surveillance, China

Genotypic and epidemiologic trends of norovirus outbreaks in the United States

Epidemiology of gastroenteritis viruses in Japan: prevalence, seasonality, and outbreak

Bureau of Disease Prevention and Control, National Health Commission of the People's Republic of China. Criterion for reporting infectious diseases in schools and child-care institutions

Evolutionary dynamics of GII.4 noroviruses over a 34-year period

Rapid evolution of pandemic noroviruses of the GII. 4 lineage

Molecular evolutionary analyses of the RNA-dependent RNA polymerase region in norovirus genogroup II