Innate Susceptibility to Norovirus Infections Influenced by FUT2 Genotype in a United States Pediatric Population.
BACKGROUND
Norovirus is a leading cause of acute gastroenteritis (AGE). Noroviruses bind to gut histo-blood group antigens (HBGAs), but only 70%-80% of individuals have a functional copy of the FUT2 ("secretor") gene required for gut HBGA expression; these individuals are known as "secretors." Susceptibility to some noroviruses depends on FUT2 secretor status, but the population impact of this association is not established.


METHODS
From December 2011 to November 2012, active AGE surveillance was performed at 6 geographically diverse pediatric sites in the United States. Case patients aged <5 years were recruited from emergency departments and inpatient units; age-matched healthy controls were recruited at well-child visits. Salivary DNA was collected to determine secretor status and genetic ancestry. Stool was tested for norovirus by real-time reverse transcription polymerase chain reaction. Norovirus genotype was then determined by sequencing.


RESULTS
Norovirus was detected in 302 of 1465 (21%) AGE cases and 52 of 826 (6%) healthy controls. Norovirus AGE cases were 2.8-fold more likely than norovirus-negative controls to be secretors (P < .001) in a logistic regression model adjusted for ancestry, age, site, and health insurance. Secretors comprised all 155 cases and 21 asymptomatic infections with the most prevalent norovirus, GII.4. Control children of Meso-American ancestry were more likely than children of European or African ancestry to be secretors (96% vs 74%; P < .001).


CONCLUSIONS
FUT2 status is associated with norovirus infection and varies by ancestry. GII.4 norovirus exclusively infected secretors. These findings are important to norovirus vaccine trials and design of agents that may block norovirus-HBGA binding.
Cincinnati Children's Hospital Medical Center University of Cincinnati Medical Scientist Training Program University of Cincinnati Molecular Epidemiology in Children's Environmental Health Training Program, Ohio.
Rebecca L
RL
Currier
Centers for Disease Control and Prevention, Atlanta, Georgia.
Daniel C
DC
Payne
Cincinnati Children's Hospital Medical Center.
Mary A
MA
Staat
Children's Mercy Hospitals and Clinics, Kansas City School of Medicine, University of Missouri-Kansas City.
Rangaraj
R
Selvarangan
Centers for Disease Control and Prevention, Atlanta, Georgia Atlanta Research and Education Foundation, Decatur, Georgia.
S Hannah
SH
Shirley
Vanderbilt University Medical Center, Nashville, Tennessee.
Natasha
N
Halasa
Baylor College of Medicine, Houston, Texas.
Julie A
JA
Boom
Seattle Children's Research Institute, Washington.
Janet A
JA
Englund
University of Rochester School of Medicine and Dentistry, New York.
Peter G
PG
Szilagyi
Children's Mercy Hospitals and Clinics, Kansas City School of Medicine, University of Missouri-Kansas City.
Christopher J
CJ
Harrison
Seattle Children's Research Institute, Washington.
Eileen J
EJ
Klein
University of Rochester School of Medicine and Dentistry, New York.
Geoffrey A
GA
Weinberg
Centers for Disease Control and Prevention, Atlanta, Georgia.
Mary E
ME
Wikswo
Centers for Disease Control and Prevention, Atlanta, Georgia.
Umesh
U
Parashar
Centers for Disease Control and Prevention, Atlanta, Georgia.
Jan
J
Vinjé
Cincinnati Children's Hospital Medical Center.
Ardythe L
AL
Morrow
D017250:Caliciviridae Infections / Q000235:genetics* / Q000276:immunology*; D016022:Case-Control Studies; D002675:Child, Preschool; D005243:Feces / Q000821:virology; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D029322:Norovirus / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D014481:United States; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase
FUT2; diarrhea; gastroenteritis; histo-blood group antigens; norovirus