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Title: Innate Resistance and Susceptibility to Norovirus Infection

The notion that certain individuals appear more or less susceptible to infections or to specific microbes is not new, but, until recently, it was assumed that clinical outcome of an infection was mainly owing to virulence factors of the microorganism. Relatively little attention has been given to host genetic factors involved in innate or adaptive immunity or expression of pathogen receptors. A remarkable example of susceptibility dependence is the strong Mendelian trait resistance to the most common noroviruses among individuals with a nonsense mutation in chromosome 19. Norovirus is recognized as the leading cause of gastroenteritis worldwide, affecting children and adults alike. Noroviruses are highly contagious and genetically diverse RNA viruses, but not all individuals are susceptible to infection to the same norovirus genotypes. Presence of histo-blood group antigens (HBGAs) on gut epithelial surfaces is essential for susceptibility to many norovirus genotypes. The synthesis of these HBGAs, specifically of the ABH and Lewis families, requires the use of several fucosyl and glycosyltransferases encoded by the FUT2, FUT3, and ABH genes. Polymorphisms in these genes vary considerably depending on ethnicity, with a homozygous nonsense mutation (individuals called non-secretors) in the FUT2 gene occurring in approximately 5%–50% of different populations worldwide. Secretormore » status also affects gut microbiota composition, including HBGA-expressing bacteria and bacteria inducing fucosylation in the gut. These could be intermediary factors that govern norovirus susceptibility.« less
Authors:
 [1] ;  [1] ;  [2] ;  [2] ;  [1] ;  [3]
  1. Linkoping Univ., Linkoping (Sweden). Division of Molecular Virology, Dept. of Clinical and Experimental Medicine (IKE)
  2. Centers for Disease Control and Prevention, Atlanta, GA (United States). Division of Viral Diseases
  3. Univ. of Kentucky, Lexington, KY (United States)
Publication Date:
Type:
Accepted Manuscript
Journal Name:
PLoS Pathogens
Additional Journal Information:
Journal Volume: 12; Journal Issue: 4; Journal ID: ISSN 1553-7374
Publisher:
Public Library of Science
Research Org:
Linkoping Univ., Linkoping (Sweden); Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Org:
USDOE; Center for Disease Control (CDC); Swedish Foundation for Strategic Research
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES
OSTI Identifier:
1378493