title: Genotype distribution of norovirus around the emergence of Sydney_2012 and the antigenic drift of contemporary GII.4 epidemic strains.
abstract: BACKGROUND
  The pattern of epochal evolution of NoV is ongoing, while novel GII.4 variants emerge and cause new pandemics. Since, the emergence in March 2012, Sydney_2012 had replaced GII.4-2009 as the primary NoV strain in most countries in the northern hemisphere by November 2012.
  
  
  OBJECTIVE
  To determine the genotype distribution around the emergence of Sydney_2012 and to investigate the underlying evolution mechanisms of the contemporary GII.4 strains.
  
  
  METHODS
  From January 2012 to December 2013, molecular epidemiology of norovirus in 846 adults (≥16 years) in Shanghai were conducted. The VP1 proteins of the contemporary GII.4 strains (Den_Haag_2006b, New_Orleans_2009 and Sydney_2012) were expressed in vitro and purified. Receptor binding patterns of these three epidemic strains were determined through histo-blood group antigen (HBGA) binding assays. Convalescent serum from patients infected with GII.4 epidemic strains were employed to investigate the role of antigenic drift in the persistence of GII.4 epidemic strains through receptor-binding blockade assays.
  
  
  RESULTS
  Epidemiological studies revealed that Sydeny_2012 has completely replaced Den_Haag_2006b and New_Orleans_2009 and has been the dominant circulating strain in Shanghai since its emergence in October 2012. Interestingly, Den_Haag_2006b and New_Orleans_2009 have been co-circulating in Shanghai before the emergence of Sydeny_2012. The contemporary GII.4 epidemic norovirus strains displayed commonly high tropism to the histo-blood group antigen receptors, whereas Sydeny_2012 was antigenically different from Den_Haag_2006b and New_Orleans_2009.
  
  
  CONCLUSIONS
  Antigenic drift, rather than receptor switch, played a key role in the emergence and spreading of Sydney_2012. The contemporary GII.4 strains were evolving via epochal evolution without altered ligand binding profiles.
authors.affiliation: Department of Laboratory Medicine, Shanghai First Maternity and Infant Hospital, Tongji University, Shanghai, China; Department of Clinical Laboratory, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: zhangjun@51mch.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Department of Clinical Laboratory, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Pathogen Diagnosis and Biosafety, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: Zhaoqin
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Pathogen Diagnosis and Biosafety, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: Wanju
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Shanghai First Maternity and Infant Hospital, Tongji University, Shanghai, China.
authors.forename: Huifen
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Fangxing
authors.initials: F
authors.lastname: Qian
authors.affiliation: Department of Pathogen Diagnosis and Biosafety, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: Haili
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: Moying
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pathogen Diagnosis and Biosafety, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: ywhu0117@126.com.
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Lab of Medical Molecular Virology, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D017250:Caliciviridae Infections / Q000453:epidemiology* / Q000821:virology*; D002681:China / Q000453:epidemiology; D058872:Epidemics; D005260:Female; D040961:Genetic Drift; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D029322:Norovirus / Q000145:classification* / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D015678:Viral Structural Proteins / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D011991:Receptors, Virus; D015678:Viral Structural Proteins
keywords: Antigenic variation; GII.4 norovirus; Molecular epidemiology; Receptor switch; Sydney_2012