Nature Medicine
9, 548 - 553 (2003)
Published online: 14 April 2003; | doi:10.1038/nm860
Human susceptibility and resistance to Norwalk virus infectionLisa Lindesmith1, Christine Moe2, 7, Severine Marionneau3, 7, Nathalie Ruvoen3, 6, Xi Jiang4, Lauren Lindblad5, Paul Stewart5, Jacques LePendu3
& Ralph Baric11
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
2
Department of International Health, Emory University, Atlanta, Georgia, USA
3
Institute of Biology, Nantes, France
4
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
5
Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, USA
6
Ecole Nationale Vétérinaire de Nantes, Nantes, France
7
C.M. and S.M. contributed equally to this study.
Correspondence should be addressed to Ralph Baric rbaric@sph.unc.eduInfectious diseases have influenced population genetics and the evolution of the structure of the human genome in part by selecting for host susceptibility alleles that modify pathogenesis. Norovirus infection is associated with  90% of epidemic non-bacterial acute gastroenteritis worldwide. Here, we show that resistance to Norwalk virus infection is multifactorial. Using a human challenge model, we showed that 29% of our study population was homozygous recessive for the  (1,2)fucosyltransferase gene (FUT2) in the ABH histo-blood group family and did not express the H type-1 oligosaccharide ligand required for Norwalk virus binding. The FUT2 susceptibility allele was fully penetrant against Norwalk virus infection as none of these individuals developed an infection after challenge, regardless of dose. Of the susceptible population that encoded a functional FUT2 gene, a portion was resistant to infection, suggesting that a memory immune response or some other unidentified factor also affords protection from Norwalk virus infection.
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REFERENCE
Antigens: Carbohydrates
Nature Encyclopaedia of Life Sciences
Caliciviruses
Nature Encyclopaedia of Life Sciences
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