title: Predicting susceptibility to norovirus GII.4 by use of a challenge model involving humans.
abstract: BACKGROUND
  GII.4 is the predominant norovirus genotype worldwide. Challenge models involving humans have shown the association of human histo-blood group antigens (HBGAs) and susceptibility to infection with Norwalk virus (GI.1 norovirus), but the association of HBGAs and infection with other noroviruses is based on results of epidemiological studies. We performed the first GII.4 challenge study involving humans and prospectively evaluated the relationship between HBGAs and norovirus infection and associated illness.
  
  
  METHODS
  Forty healthy adults (23 secretors and 17 nonsecretors of HBGAs) were challenged with 5 10(4) reverse-transcription polymerase chain reaction (RT-PCR) units of GII.4 norovirus. Subjects were assessed daily for clinical illness, and stool specimens were evaluated for norovirus by RT-PCR. Infection was defined by detection of norovirus and/or seroconversion to GII.4 antibody.
  
  
  RESULTS
  Of the 23 secretors, 16 (70%) were infected with norovirus, 13 (57%) became ill (characterized by vomiting and/or diarrhea), and 12 (52%) developed norovirus-associated illness. In contrast, only 1 nonsecretor (5.9%) became ill, and another nonsecretor shed virus for a single day (P < .001 for each variable, compared with secretors). Infection occurred in secretors regardless of ABO blood group. Illness was mild to moderate in severity and lasted 1-3 days.
  
  
  CONCLUSIONS
  Secretor status determined the susceptibility to norovirus GII.4 challenge. This human challenge model should be useful for evaluating norovirus vaccines and antiviral agents. Clinical trials registration. NCT01322503.
authors.affiliation: Division Infectious Diseases, Cincinnati Children's Hospital Medical Center, OH, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Frenck
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.forename: Ming
authors.initials: M
authors.lastname: Xia
authors.forename: Pengwei
authors.initials: P
authors.lastname: Huang
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhong
authors.forename: Susan
authors.initials: S
authors.lastname: Parker
authors.forename: Michelle
authors.initials: M
authors.lastname: Dickey
authors.forename: Monica
authors.initials: M
authors.lastname: McNeal
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D001789:Blood Group Antigens / Q000032:analysis*; D017250:Caliciviridae Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D004198:Disease Susceptibility; D005243:Feces / Q000821:virology; D005260:Female; D005838:Genotype; D006805:Human Experimentation; D006801:Humans; D008297:Male; D008875:Middle Aged; D029322:Norovirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D001789:Blood Group Antigens