title: Both Lewis and secretor status mediate susceptibility to rotavirus infections in a rotavirus genotype-dependent manner.
abstract: BACKGROUND
  The live oral rotavirus (RV) vaccines have shown a reduced efficacy in Africa. Recent in vitro studies have shown binding of the RV surface protein (VP4) to histo-blood group antigens (HBGAs) in an RV genotype-dependent manner, suggesting them to be putative receptors for RV. The diversity of HBGA phenotypes in different ethnic populations, combined with prevalence/absence of specific RV genotypes, led us to hypothesize whether the genetic variations in HBGAs in a population limit susceptibility to certain RV genotypes, plausibly leading to reduced vaccine efficacy.
  
  
  METHODS
  Association between HBGAs status and susceptibility to RV P genotypes was investigated in children in Burkina Faso and Nicaragua. In total, 242 children with diarrhea in Burkina Faso and Nicaragua were investigated, 93 of whom were RV positive.
  
  
  RESULTS
  In Burkina Faso, the P[8] RV strains (n = 27) infected only Lewis- and secretor-positive children (27/27; P < .0001), but no Lewis-negative children. In contrast, the P[6] strains (n = 27) infected predominantly Lewis-negative children (n = 18; P < .0001) but also Lewis-positive children, irrespective of their secretor status. The results from Nicaragua confirmed that all P[8]-infected children (n = 22) were secretor Lewis positive.
  
  
  CONCLUSIONS
  As VP4 of genotype P[8] is a component of current RV vaccines, our finding that Lewis-negative children are resistant to P[8] strains provides a plausible explanation for the reduced vaccine efficacy in populations with a high percentage of Lewis-negative individuals, such as in Africa. Furthermore, our findings provide a plausible explanation as to why P[6] RV strains are more common in Africa.
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Medical Faculty, Linköping University, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Nordgren
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Medical Faculty, Linköping University, Sweden.
authors.forename: Sumit
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Microbiology, University of León, Nicaragua.
authors.forename: Filemon
authors.initials: F
authors.lastname: Bucardo
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg.
authors.forename: Waqas
authors.initials: W
authors.lastname: Nasir
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gökçe
authors.initials: G
authors.lastname: Günaydın
authors.affiliation: Centre de Recherche Biomoléculaire Pietro Annigoni Saint Camille CERBA/LABIOGENE, Université de Ouagadougou, Burkina Faso.
authors.forename: Djeneba
authors.initials: D
authors.lastname: Ouermi
authors.affiliation: Centre de Recherche Biomoléculaire Pietro Annigoni Saint Camille CERBA/LABIOGENE, Université de Ouagadougou, Burkina Faso.
authors.forename: Leon W
authors.initials: LW
authors.lastname: Nitiema
authors.affiliation: Department of Family Medicine, School of Medicine, University of North Carolina at Chapel Hill.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Becker-Dreps
authors.affiliation: Centre de Recherche Biomoléculaire Pietro Annigoni Saint Camille CERBA/LABIOGENE, Université de Ouagadougou, Burkina Faso.
authors.forename: Jacques
authors.initials: J
authors.lastname: Simpore
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg.
authors.forename: Göran
authors.initials: G
authors.lastname: Larson
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Medical Faculty, Linköping University, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Svensson
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D002050:Burkina Faso / Q000453:epidemiology; D002675:Child, Preschool; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007983:Lewis Blood Group Antigens / Q000235:genetics*; D009527:Nicaragua / Q000453:epidemiology; D012401:Rotavirus / Q000235:genetics*; D012400:Rotavirus Infections / Q000453:epidemiology / Q000235:genetics / Q000821:virology*
chemical_list: D000017:ABO Blood-Group System; D007983:Lewis Blood Group Antigens
keywords: Lewis; histo–blood group antigen; rotavirus; susceptibility; vaccine
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