Human susceptibility and resistance to Norwalk virus infection.
Infectious 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 approximately 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 alpha(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.
Lindesmith
Lisa
L
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Moe
Christine
C
Marionneau
Severine
S
Ruvoen
Nathalie
N
Jiang
Xi
X
Lindblad
Lauren
L
Stewart
Paul
P
LePendu
Jacques
J
Baric
Ralph
R
D000017:ABO Blood-Group System / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis; D017250:Caliciviridae Infections / Q000276:immunology*; D004311:Double-Blind Method; D005647:Fucosyltransferases / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007156:Immunologic Memory; D009663:Norwalk virus / Q000276:immunology*; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D000017:ABO Blood-Group System; D000914:Antibodies, Viral; D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase