Changing predominance of norovirus strains in children with acute gastroenteritis in Shanghai, 2018–2021

Lijuan Lu; Yuanyun Ao; Ran Jia; Huaqing Zhong; Pengcheng Liu; Menghua Xu; Liyun Su; Lingfeng Cao; Jin Xu

doi:10.1016/j.virs.2023.08.005

October 2023

Lijuan Lu, Yuanyun Ao, Ran Jia, Huaqing Zhong, Pengcheng Liu, Menghua Xu, Liyun Su, Lingfeng Cao and Jin Xu. Changing predominance of norovirus strains in children with acute gastroenteritis in Shanghai, 2018–2021[J]. Virologica Sinica, 2023, 38(5): 671-679. doi: 10.1016/j.virs.2023.08.005

Citation: Lijuan Lu, Yuanyun Ao, Ran Jia, Huaqing Zhong, Pengcheng Liu, Menghua Xu, Liyun Su, Lingfeng Cao, Jin Xu. Changing predominance of norovirus strains in children with acute gastroenteritis in Shanghai, 2018–2021 .VIROLOGICA SINICA, 2023, 38(5) : 671-679. http://dx.doi.org/10.1016/j.virs.2023.08.005

2018-2021年上海地区急性胃肠炎儿童中诺如病毒优势株的变迁

卢丽娟 ^a ,
敖元云 ^a ,
贾然 ^a ,
钟华清 ^a ,
柳鹏程 ^a ,
徐梦华 ^a ,
苏犁云 ^a ,
曹凌峰 ^a ,
徐锦 ^a,b,,

a. 复旦大学附属儿科医院;
b. 上海市重大传染病和生物安全研究院

通讯作者： 徐锦, jinxu_125@163.com
收稿日期： 2023-04-14
录用日期： 2023-08-17

摘要

目的诺如病毒（Norovirus, NoV）是引起儿童急性胃肠炎（Acute gastroenteritis, AGE）的主要病原体之一，现尚无有效疫苗。我们研究了2018年至2021年上海地区AGE儿童中NoV的分子流行病学特点，以监测上海地区AGE儿童中NoV基因型别的变迁。方法收集2018年1月至2021年12月前来复旦大学附属儿科医院门急诊就诊的AGE儿童粪便样本1545例。采用NoV RdRp-VP1双基因分型方法检测粪便样本中的NoV，并将PCR产物进行一代测序。通过MEGA 6.06软件构建生物系统进化树，确定NoV的P基因型和VP1基因型，最终确定NoV的组合基因型。同时，收集NoV感染儿童的病史信息进行分析。结果 2018-2021年期间上海地区AGE儿童中NoV的总体检出率为11.9%（181/1545），年度检出率分别为9.4%（36/381）、13.6%（29/213）、5.8%（13/226）和14.2%（103/725）。值得注意的是，2020年NoV的流行率明显低于2018-2019年（10.9%，65/594）（p=0.023）和2021年（14.2%，103/725）（p=0.000）。根据VP1基因序列分型，181株NoV被分为GI组（1.1%，2/181）、GII组（98.3%，178/181）和GIX组（0.6%，1/181）。最常见的VP1基因型为GII.4 Sydney_2012（63.5%，115/181），其次是GII.3（19.9%，36/181）和GII.2（9.4%，17/181）。根据RdRp基因序列分型发现，174株NoV的P分型成功，最主要的P基因型为GII.P16（44.8%，78/174），其次是GII.P31（25.9%，45/174）和GII.P12（21.3%，37/174）。P和VP1基因型均分型成功的174株NoV中，GII.4 Sydney_2012[P16]（36.8%，64/174）是最主要的组合型别，其次为GII.4 Sydney_2012[P31]（25.3%，44/174）、GII.3[P12]（20.1%，35/174）和GII.2[P16]（8.0%，14/174），且重组株占96.6% (168/174)。每年主要流行的基因型有所不同。2018年，GII.3[P12]的检出率与GII.4 Sydney_2012[P31]相同，均占36.1%（13/36），其次为GII.2[P16]（8.3%，3/36）。GII.4 Sydney_2012[P31]（51.9%，14/27）是2019年最常见的基因型，其次为GII.3[P12]（48.1%，13/27）。而在2020和2021年，GII.4 Sydney_2012[P16]成为最主要的流行株，分别占38.5%（5/13）和59.2%（58/98）；其次均为GII.4 Sydney_2012[P31]型，分别占23.1%（3/13）和14.3%（14/98）。结论本研究首次报道了上海地区新冠疫情前后NoV在AGE儿童中的流行情况，为NoV疫苗的研发及上海地区儿童NoV疫苗的接种策略提供了理论基础。
- 诺如病毒
- , 急性胃肠炎
- , 儿童
- , 基因型
- , 重组株

Changing predominance of norovirus strains in children with acute gastroenteritis in Shanghai, 2018–2021

Lijuan Lu ^a ,
Yuanyun Ao ^a ,
Ran Jia ^a ,
Huaqing Zhong ^a ,
Pengcheng Liu ^a ,
Menghua Xu ^a ,
Liyun Su ^a ,
Lingfeng Cao ^a ,
Jin Xu ^a,b,,

a. Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201100, China;
b. Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, 201100, China

Corresponding author: Jin Xu, jinxu_125@163.com
Received Date: 14 April 2023
Accepted Date: 17 August 2023

Abstract

Norovirus (NoV) is a major pathogen that causes acute gastroenteritis (AGE) in people of all ages, especially in children. In this study, we investigated the molecular epidemiological characteristics of NoV in children with AGE in Shanghai from 2018 to 2021. The overall detection rate of NoV was 11.9% (181/1545), with annual detection rates of 9.4% (36/381), 13.6% (29/213), 5.8% (13/226) and 14.2% (103/725), respectively. Of note, the prevalence of NoV in 2020 was significantly lower than that in 2018-2019 (10.9%, 65/594) (P=0.023) and 2021 (14.2%, 103/725) (P=0.000). The 181 NoV strains identified in this study were classified into the GI group (1.1%, 2/181), GII group (98.3%, 178/181) and GIX group (0.6%, 1/181) according to the VP1 gene. The most common NoV VP1 genotype was GII.4 Sydney_2012 (63.5%, 115/181), followed by GII.3 (19.9%, 36/181) and GII.2 (9.4%, 17/181). For P genotypes, 174 strains were sequenced successfully according to the RdRp gene, and the predominant genotype was GII.P16 (44.8%, 78/174), followed by GII.P31 (25.9%, 45/174) and GII.P12 (21.3%, 37/174). Among the 174 cases, GII.4 Sydney_2012[P16] (36.8%, 64/174) was the dominant genotype, followed by GII.4 Sydney_2012[P31] (25.3%, 44/174), GII.3[P12] (20.1%, 35/174) and GII.2[P16] (8.0%, 14/174). In particular, the dominant genotypes in Shanghai changed from GII.4 Sydney_2012[P31] in 2018-2019 to GII.4 Sydney_2012[P16] in 2020-2021. This is the first report to describe the epidemiological changes in NoV infection before and during the COVID-19 pandemic in Shanghai. These data highlight the importance of continuous surveillance for NoV in children with AGE in Shanghai.
- Norovirus (NoV)
- , Acute gastroenteritis
- , Children
- , Genotype
- , Recombination

References
1. Ao Y, Wang J, Ling H, He Y, Dong X, Wang X, Peng J, Zhang H, Jin M, Duan Z. 2017. Norovirus GII.P16/GII.2-associated gastroenteritis, China, 2016. Emerg Infect Dis, 23:1172-1175.
2. Bartsch SM, Lopman BA, Ozawa S, Hall AJ, Lee BY. 2016. Global economic burden of norovirus gastroenteritis. PLoS One, 11:e0151219.
3. Campillay-Veliz CP, Carvajal JJ, Avellaneda AM, Escobar D, Covian C, Kalergis AM, Lay MK. 2020. Human norovirus proteins:Implications in the replicative cycle, pathogenesis, and the host immune response. Front Immunol, 11:961.
4. Cannon JL, Barclay L, Collins NR, Wikswo ME, Castro CJ, Magana LC, Gregoricus N, Marine RL, Chhabra P, Vinje J. 2017. Genetic and epidemiologic trends of norovirus outbreaks in the United States from 2013 to 2016 demonstrated emergence of novel GII.4 recombinant viruses. J Clin Microbiol, 55:2208-2221.
5. Cao RR, Ma XZ, Li WY, Wang BN, Yang Y, Wang HR, Kuang Y, You JZ, Zhao ZY, Ren M, Zhou LL, Li MY. 2021. Epidemiology of norovirus gastroenteritis in hospitalized children under five years old in western China, 2015-2019. J Microbiol Immunol Infect, 54:918-925.
6. Chen C, Yan JB, Wang HL, Li P, Li KF, Wu B, Zhang H. 2018. Molecular epidemiology and spatiotemporal dynamics of norovirus associated with sporadic acute gastroenteritis during 2013-2017, Zhoushan islands, China. PLoS One, 13:e0200911.
7. Chen LN, Wang SJ, Wang SM, Fu XL, Zheng WJ, Hao ZY, Zhou HS, Zhang XJ, Zhao YL, Qiu C, von Seidlein L, Qiu TY, Wang XY. 2023. Molecular epidemiology analysis of symptomatic and asymptomatic norovirus infections in Chinese infants. Virol J, 20(1):60.
8. Cheung SKC, Kwok K, Zhang LY, Mohammad KN, Lui GCY, Lee N, Nelson EAS, Lai RWM, Leung TF, Chan PKS, Chan MC. 2019. Higher Viral Load of Emerging Norovirus GII.P16-GII.2 than Pandemic GII.4 and Epidemic GII.17, Hong Kong, China. Emerg Infect Dis, 25(1):119-122.
9. Chhabra P, de Graaf M, Parra GI, Chan MC, Green K, Martella V, Wang Q, White PA, Katayama K, Vennema H, Koopmans MPG, Vinje J. 2019. Updated classification of norovirus genogroups and genotypes. J Gen Virol, 100:1393-1406.
10. Chhabra P, Graaf M, Parra GI, Chan MC, Green K, Martella V, Wang Q, White PA, Katayama K, Vennema H, Koopmans MPG, Vinjé J. 2020. Corrigendum:Updated classification of norovirus genogroups and genotypes. J Gen Virol, 101(8):893.
11. Choi YS, Koo ES, Kim MS, Choi JD, Shin Y, Jeong YS. 2017. Re-emergence of a gii.4 norovirus sydney 2012 variant equipped with GII.P16 RdRp and its predominance over novel variants of GII.17 in south Korea in 2016. Food Environ Virol, 9:168-178.
12. Deval J, Jin Z, Chuang YC, Kao CC. 2017. Structure(s), function(s), and inhibition of the RNA-dependent RNA polymerase of noroviruses. Virus Res, 234:21-33.
13. Ennuschat N, Hartel S, Pietsch C, Liebert UG. 2021. Norovirus epidemiology and genetic diversity in Leipzig, Germany during 2013-2017. Viruses, 13.
14. Fang Y, Dong Z, Liu Y, Wang W, Hou M, Wu J, Wang L, Zhao Y. 2021. Molecular epidemiology and genetic diversity of norovirus among hospitalized children with acute gastroenteritis in Tianjin, China, 2018-2020. BMC Infect Dis, 21:682.
15. Farahmand M, Moghoofei M, Dorost A, Shoja Z, Ghorbani S, Kiani SJ, Khales P, Esteghamati A, Sayyahfar S, Jafarzadeh M, Minaeian S, Khanaliha K, Naghdalipour M, Tavakoli A. 2022. Global prevalence and genotype distribution of norovirus infection in children with gastroenteritis:A meta-analysis on 6 years of research from 2015 to 2020. Rev Med Virol, 32:e2237.
16. Fu J, Ai J, Bao C, Zhang J, Wu Q, Zhu L, Hu J, Xing Z. 2021. Evolution of the GII.3[P12] norovirus from 2010 to 2019 in Jiangsu, China. Gut Pathog, 13:34.
17. Fu J, Ai J, Jin M, Jiang C, Zhang J, Shi C, Lin Q, Yuan Z, Qi X, Bao C, Tang F, Zhu Y. 2015. Emergence of a new GII.17 norovirus variant in patients with acute gastroenteritis in Jiangsu, China, September 2014 to March 2015. Euro Surveill, 20:21157.
18. Han J, Wu X, Chen L, Fu Y, Xu D, Zhang P, Ji L. 2018. Emergence of norovirus GII.P16- GII.2 strains in patients with acute gastroenteritis in Huzhou, China, 2016-2017. BMC Infect Dis, 18:342.
19. Iritani N, Kaida A, Abe N, Sekiguchi J, Kubo H, Takakura K, Goto K, Ogura H, Seto Y. 2012. Increase of GII.2 norovirus infections during the 2009-2010 season in Osaka city, Japan. J Med Virol, 84:517-525.
20. Jin M, Wu S, Kong X, Xie H, Fu J, He Y, Feng W, Liu N, Li J, Rainey JJ, Hall AJ, Vinje J, Duan Z. 2020. Norovirus outbreak surveillance, China, 2016-2018. Emerg Infect Dis, 26:437-445.
21. Jones BJ, Flint J, Collins J, White PA, Lun JH, Durrheim DN. 2018. Gastroenteritis outbreak at a health function caused by an emerging recombinant strain of norovirus GII.P16/GII.4 sydney 2012, Australia. Epidemiol Infect, 146:970-971.
22. Kendra JA, Tohma K, Parra GI. 2022. Global and regional circulation trends of norovirus genotypes and recombinants, 1995-2019:A comprehensive review of sequences from public databases. Rev Med Virol, 32:e2354.
23. Kojima S, Kageyama T, Fukushi S, Hoshino FB, Shinohara M, Uchida K, Natori K, Takeda N, Katayama K. Genogroup-specific PCR primers for detection of Norwalk-like viruses. J Virol Methods, 2002;100(1-2):107-14.
24. Li J, Zhang L, Zou W, Yang Z, Zhan J, Cheng J. 2023. Epidemiology and genetic diversity of norovirus GII genogroups among children in Hubei, China, 2017-2019. Virol Sin, 38(3):351-362.
25. Lopman BA, Steele D, Kirkwood CD, Parashar UD. 2016. The vast and varied global burden of norovirus:Prospects for prevention and control. PLoS Med, 13:e1001999.
26. Lu J, Fang L, Sun L, Zeng H, Li Y, Zheng H, Wu S, Yang F, Song T, Lin J, Ke C, Zhang Y, Vinje J, Li H. 2017. Association of GII.P16- GII.2 recombinant norovirus strain with increased norovirus outbreaks, Guangdong, China, 2016. Emerg Infect Dis, 23:1188-1190.
27. Lu LJ, Zhong HQ, Xu MH, Su LY, Cao LF, Jia R, Xu J. 2019. Genetic diversity and epidemiology of genogroup ii noroviruses in children with acute sporadic gastroenteritis in Shanghai, China, 2012-2017. BMC Infect Dis, 19:736.
28. Lu LJ, Zhong HQ, Xu MH, Su LY, Cao LF, Dong NN, Xu J. 2014. Molecular epidemiology of human calicivirus infections in children with acute diarrhea in Shanghai:a retrospective comparison between inpatients and outpatients treated between 2006 and 2011. Arch Virol, 159(7):1613-1621.
29. Lun JH, Hewitt J, Yan GJH, Enosi Tuipulotu D, Rawlinson WD, White PA. 2018. Recombinant GII.P16/GII.4 sydney 2012 was the dominant norovirus identified in Australia and New Zealand in 2017. Viruses, 10.
30. Mahar JE, Bok K, Green KY, Kirkwood CD. 2013. The importance of intergenic recombination in norovirus GII.3 evolution. J Virol, 87:3687-3698.
31. Mikounou Louya V, Vouvoungui C, Koukouikila-Koussounda F, Veas F, Kobawila SC, Ntoumi F. 2019. Molecular characterization of norovirus infection responsible for acute diarrhea in congolese hospitalized children under five years old in Brazzaville, republic of Congo. Int J Infect Dis, 88:41-48.
32. Ozaki K, Matsushima Y, Nagasawa K, Motoya T, Ryo A, Kuroda M, Katayama K, Kimura H. 2018. Molecular evolutionary analyses of the RNA-dependent RNA polymerase region in norovirus genogroup II. Front Microbiol, 9:3070.
33. Parra GI. 2019. Emergence of norovirus strains:A tale of two genes. Virus Evol, 5:vez048.
34. Robilotti E, Deresinski S, Pinsky BA. 2015. Norovirus. Clin Microbiol Rev, 28:134-164.
35. Saupe AA, Rounds J, Sorenson A, Hedeen N, Bagstad E, Reinberg R, Wagley AG, Cebelinski E, Smith K. 2021. Outbreak of norovirus gastroenteritis associated with ice cream contaminated by frozen raspberries from China-Minnesota, United States, 2016. Clin Infect Dis, 73:e3701-e3707.
36. Smertina E, Urakova N, Strive T, Frese M. 2019. Calicivirus RNA-dependent RNA polymerases:evolution, structure, protein dynamics, and function. Front Microbiol, 10:1280.
37. Utsumi T, Lusida MI, Dinana Z, Wahyuni RM, Soegijanto S, Soetjipto, Athiyyah AF, Sudarmo SM, Ranuh RG, Darma A, Juniastuti, Yamani LN, Doan YH, Shimizu H, Ishii K, Matsui C, Deng L, Abe T, Katayama K, Shoji I. 2021. Molecular epidemiology and genetic diversity of norovirus infection in children hospitalized with acute gastroenteritis in east Java, Indonesia in 2015-2019. Infect Genet Evol, 88:104703.
38. Vakulenko YA, Orlov AV, Lukashev AN. 2023. Patterns and temporal dynamics of natural recombination in noroviruses. Viruses, 15.
39. van Beek J, de Graaf M, Al-Hello H, Allen DJ, Ambert-Balay K, Botteldoorn N, Brytting M, Buesa J, Cabrerizo M, Chan M, Cloak F, Di Bartolo I, Guix S, Hewitt J, Iritani N, Jin M, Johne R, Lederer I, Mans J, Martella V, Maunula L, McAllister G, Niendorf S, Niesters HG, Podkolzin AT, Poljsak-Prijatelj M, Rasmussen LD, Reuter G, Tuite G, Kroneman A, Vennema H, Koopmans MPG, NoroNet. 2018. Molecular surveillance of norovirus, 2005-16:An epidemiological analysis of data collected from the noronet network. Lancet Infect Dis, 18:545-553.
40. Wang J, Jin M, Zhang H, Zhu Y, Yang H, Yao X, Chen L, Meng J, Hu G, He Y, Duan Z. 2021. Norovirus GII.2[P16] strain in Shenzhen, China:A retrospective study. BMC Infect Dis, 21:1122.
41. Wei N, Ge J, Tan C, Song Y, Wang S, Bao M, Li J. 2021. Epidemiology and evolution of norovirus in china. Hum Vaccin Immunother, 17:4553-4566.
42. Zhang N, Shi T, Zhong H, Guo Y. 2020. Covid-19 prevention and control public health strategies in Shanghai, China. J Public Health Manag Pract, 26:334-344.
43. Zheng GL, Zhu ZX, Cui JL, Yu JM. 2022. Evolutionary analyses of emerging GII.2[P16] and GII.4 sydney[P16] noroviruses. Virus Evol, 8:veac030.
44. Zhou HL, Zhen SS, Wang JX, Zhang CJ, Qiu C, Wang SM, Jiang X, Wang XY. 2017. Burden of acute gastroenteritis caused by norovirus in China:A systematic review. J Infect, 75(3):216-224.
Proportional views
Electronic Supplementary Material

10.1016j.virs.2023.08.005-ESM.rtf