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Both Lewis and Secretor Status Mediate Susceptibility to Rotavirus Infections in a Rotavirus Genotype-Dependent Manner
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
University of Leon, Nicaragua.
University of Gothenburg, Sweden.
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2014 (English)In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 59, no 11, 1567-1573 p.Article in journal (Refereed) Published
Abstract [en]

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 less than .0001), but no Lewis-negative children. In contrast, the P[6] strains (n = 27) infected predominantly Lewis-negative children (n = 18; P less than.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.

Place, publisher, year, edition, pages
Oxford University Press (OUP): Policy A1 - Oxford Open Option C , 2014. Vol. 59, no 11, 1567-1573 p.
Keyword [en]
rotavirus; histo-blood group antigen; Lewis; susceptibility; vaccine
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-113179DOI: 10.1093/cid/ciu633ISI: 000345841900011PubMedID: 25097083OAI: oai:DiVA.org:liu-113179DiVA: diva2:780015
Note

Funding Agencies|Swedish Research Council [8266, 3485, dnr-348-2011-7420]

Available from: 2015-01-13 Created: 2015-01-12 Last updated: 2017-12-05

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Nordgren, JohanSharma, SumitSvensson, Lennart

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