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A homozygous nonsense mutation (428G -> A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infections

Thorven, M; Grahn, A; Hedlund, K O; Johansson, H; Wahlfrid, Christer LU ; Larson, G and Svensson, L (2005) In Journal of Virology 79(24). p.15351-15355
Abstract
Noroviruses (formerly Norwalk-like viruses) are a major cause of acute gastroenteritis worldwide and are associated with a significant number of nosocomial and food-borne outbreaks. In this study we show that the human secretor FUT2 gene, which codes for an alpha(1,2)-fucosyltransferase synthesizing the H-type 1 antigen in saliva and mucosa, is associated with susceptibility to norovirus infections. Allelic polymorphism characterization at nucleotide 428 for symptomatic (n = 53) and asymptomatic (n = 62) individuals associated with nosocomial and sporadic norovirus outbreaks revealed that homozygous nonsense mutation (428G -> A) in FUT2 segregated with complete resistance for the disease. Of all symptomatic individuals, 49% were... (More)
Noroviruses (formerly Norwalk-like viruses) are a major cause of acute gastroenteritis worldwide and are associated with a significant number of nosocomial and food-borne outbreaks. In this study we show that the human secretor FUT2 gene, which codes for an alpha(1,2)-fucosyltransferase synthesizing the H-type 1 antigen in saliva and mucosa, is associated with susceptibility to norovirus infections. Allelic polymorphism characterization at nucleotide 428 for symptomatic (n = 53) and asymptomatic (n = 62) individuals associated with nosocomial and sporadic norovirus outbreaks revealed that homozygous nonsense mutation (428G -> A) in FUT2 segregated with complete resistance for the disease. Of all symptomatic individuals, 49% were homozygous (SeSe) and 51% heterozygous (Sese(428)) secretors, and none were secretor negative (se(428)se(428)), in contrast to 20% nonsecretors (se(428)se(428)) among Swedish blood donors (n = 104) (P < 0.0002) and 29% for asymptomatic individuals associated with nosocomial outbreaks (P < 0.00001). Furthermore, saliva from secretor-positive and symptomatic patients but not from secretor-negative and asymptomatic individuals bound the norovirus strain responsible for that particular outbreak. This is the first report showing that the FUT2 nonsecretor (se(428)se(428)) genotype is associated with resistance to nosocomial and sporadic outbreaks with norovirus. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Virology
volume
79
issue
24
pages
15351 - 15355
publisher
American Society for Microbiology
external identifiers
  • wos:000234276700036
  • scopus:29744442306
ISSN
1098-5514
DOI
10.1128/JVI.79.24.15351-15355.2005
language
English
LU publication?
yes
id
f33ddc0a-0c9c-4ac1-a9de-71ba6c1ed0a1 (old id 210214)
date added to LUP
2007-08-06 10:53:21
date last changed
2017-10-22 04:40:21
@article{f33ddc0a-0c9c-4ac1-a9de-71ba6c1ed0a1,
  abstract     = {Noroviruses (formerly Norwalk-like viruses) are a major cause of acute gastroenteritis worldwide and are associated with a significant number of nosocomial and food-borne outbreaks. In this study we show that the human secretor FUT2 gene, which codes for an alpha(1,2)-fucosyltransferase synthesizing the H-type 1 antigen in saliva and mucosa, is associated with susceptibility to norovirus infections. Allelic polymorphism characterization at nucleotide 428 for symptomatic (n = 53) and asymptomatic (n = 62) individuals associated with nosocomial and sporadic norovirus outbreaks revealed that homozygous nonsense mutation (428G -&gt; A) in FUT2 segregated with complete resistance for the disease. Of all symptomatic individuals, 49% were homozygous (SeSe) and 51% heterozygous (Sese(428)) secretors, and none were secretor negative (se(428)se(428)), in contrast to 20% nonsecretors (se(428)se(428)) among Swedish blood donors (n = 104) (P &lt; 0.0002) and 29% for asymptomatic individuals associated with nosocomial outbreaks (P &lt; 0.00001). Furthermore, saliva from secretor-positive and symptomatic patients but not from secretor-negative and asymptomatic individuals bound the norovirus strain responsible for that particular outbreak. This is the first report showing that the FUT2 nonsecretor (se(428)se(428)) genotype is associated with resistance to nosocomial and sporadic outbreaks with norovirus.},
  author       = {Thorven, M and Grahn, A and Hedlund, K O and Johansson, H and Wahlfrid, Christer and Larson, G and Svensson, L},
  issn         = {1098-5514},
  language     = {eng},
  number       = {24},
  pages        = {15351--15355},
  publisher    = {American Society for Microbiology},
  series       = {Journal of Virology},
  title        = {A homozygous nonsense mutation (428G -> A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infections},
  url          = {http://dx.doi.org/10.1128/JVI.79.24.15351-15355.2005},
  volume       = {79},
  year         = {2005},
}