The G428A nonsense mutation in FUT2 provides strong but not absolute protection against symptomatic GII.4 Norovirus infection: Novel GII.4 disease pattern

• Published in: PloS one 2009, Vol.4 (5)
• Main Authors: Carlsson, Beatrice, Kindberg, Elin, Buesa, Javier, Rydell, Gustaf E, Lidón, Marta Fos, Montava, Rebeca, Abu Mallouh, Reem, Grahn, Ammi, Rodríguez-Díaz, Jesús, Bellido, Juan, Arnedo, Alberto, Larson, Göran, Svensson, Lennart
• Format: Article
• Language: English
• Subjects: ABO Blood-Group System; Annan klinisk medicin; Caliciviridae Infections; classification; Codon; Disease Outbreaks; Enzyme-Linked Immunosorbent Assay; Fucosyltransferases; genetics; Genotype; Humans; Infectious Medicine; Infektionsmedicin; Lewis Blood-Group System; Microbiology in the medical area; Mikrobiologi inom det medicinska området; Nonsense; Norovirus; Other Clinical Medicine; Phylogeny; Reverse Transcriptase Polymerase Chain Reaction; Saliva; Spain; virology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0005593

In November 2004, 116 individuals in an elderly nursing home in El Grao de Castellón, Spain were symptomatically infected with genogroup II.4 (GII.4) norovirus. The global attack rate was 54.2%. Genotyping of 34 symptomatic individuals regarding the FUT2 gene revealed that one patient was, surprisingly, a non-secretor, hence indicating secretor-independent infection. Lewis genotyping revealed that Lewis-positive and negative individuals were susceptible to symptomatic norovirus infection indicating that Lewis status did not predict susceptibility. Saliva based ELISA assays were used to determine binding of the outbreak virus to saliva samples. Saliva from a secretor-negative individual bound the authentic outbreak GII.4 Valencia/2004/Es virus, but did not in contrast to secretor-positive saliva bind VLP of other strains including the GII.4 Dijon strain. Amino acid comparison of antigenic A and B sites located on the external loops of the P2 domain revealed distinct differences between the Valencia/2004/Es and Dijon strains. All three aa in each antigenic site as well as 10/11 recently identified evolutionary hot spots, were unique in the Valencia/2004/Es strain compared to the Dijon strain. To the best of our knowledge, this is the first example of symptomatic GII.4 norovirus infection of a Le(a+b-) individual homozygous for the G428A nonsense mutation in FUT2. Taken together, our study provides new insights into the host genetic susceptibility to norovirus infections and evolution of the globally dominating GII.4 viruses.