Within-host evolution results in antigenically distinct GII.4 noroviruses
      
      
        
      
      
      
      
        
          
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Debbink, Kari
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA
          
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Lindesmith, Lisa C.
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
          
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Ferris, Martin T.
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA
          
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Swanstrom, Jesica
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
          
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Beltramello, Martina
  Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
          
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Corti, Davide
  Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Humabs Biomed SA, Bellinzona, Switzerland
          
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Lanzavecchia, Antonio
  Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Institute of Microbiology, ETH Zurich, Zurich, Switzerland
          
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Baric, Ralph S.
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, USA - Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
          
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        Published in:
        
          
            
            - Journal of virology. - 2014, vol. 88, no. 13, p. 7244–7255
 
       
      
      
      
       
      
      
      
        
        English
        
        
        
          Genogroup II, genotype 4 (GII.4) noroviruses are known to rapidly evolve, with the  emergence of a new primary strain every 2 to 4 years as herd immunity to the  previously circulating strain is overcome. Because viral genetic diversity is higher in  chronic than in acute infection, chronically infected immunocompromised people have  been hypothesized to be a potential source for new epidemic GII.4 strains. However,  while some capsid protein residues are under positive selection and undergo  patterned changes in sequence variation over time, the relationships between genetic  variation and antigenic variation remains unknown. Based on previously published  GII.4 strains from a chronically infected individual, we synthetically reconstructed virus- like particles (VLPs) representing early and late isolates from a small-bowel transplant  patient chronically infected with norovirus, as well as the parental GII.4-2006b strain.  We demonstrate that intrahost GII.4 evolution results in the emergence of antigenically  distinct strains over time, comparable to the variation noted between the  chronologically predominant GII.4 strains GII.4-2006b and GII.4-2009. Our data  suggest that in some individuals the evolution that occurs during a chronic norovirus  infection overlaps with changing antigenic epitopes that are associated with  successive outbreak strains and may select for isolates that are potentially able to  escape herd immunity from earlier isolates.
        
        
       
      
      
      
        
        
        
        
        
        
        
        
        
        
        
        
        
        
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                  Medicine
                
              
            
          
        
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          Open access status
        
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          green
        
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          https://n2t.net/ark:/12658/srd1318854
        
 
   
  
  
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