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Norovirus Immunity and the Great Escape 英文参考文献
Pearls
NorovirusImmunityandtheGreatEscape
KariDebbink1,LisaC.Lindesmith2,EricF.Donaldson2,RalphS.Baric1,2*
1DepartmentofMicrobiologyandImmunology,SchoolofMedicine,UniversityofNorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica,
2DepartmentofEpidemiology,GillingsSchoolofGlobalPublicHealth,UniversityofNorthCarolinaatChapelHill,ChapelHill,NorthCarolina,UnitedStatesofAmerica
NorovirusesRepresentaSignificantWorldwide
DiseaseBurden
About20%ofpeopledonotencodeafunctionalFUT2geneand
are considered ‘‘non-secretors’’ (Figure 1D). Non-secretors are
resistant to GI.1 (Norwalk virus) infection [10]; however, some
otherNoVstrainsareknowntoinfectnon-secretors,probablyby
attachment to Lewis carbohydrates [11–14]. GII.4 strains may
predominate because the epidemic strains bind A, B, and O
secretors,representativeof80%ofthepopulation.Antibodiesthat
blockvirusbindingtoHBGAareconsidered‘‘blockadeantibod-
ies’’ and are predicted to be neutralizing. Importantly, high
prechallenge blockade antibody titers correlate with protection
frominfectionfollowingprimarychallengeandvaccination[15].
The development of more human challenge strains and thera-
peutic antibodies will be key for illuminating the complex
relationshipsamongHBGAaffinity,hostsusceptibility,shortand
long-term immunity outcomes, and the mechanism of action by
whichblockadeantibodiespreventinfection.
Noroviruses (NoVs), members of the Calicivirus family, are
small,positive-polarityRNAvirusesandthemostimportantcause
ofhumanfoodborneviralgastroenteritisworldwide.Theseviruses
cause gastrointestinal disease, resulting in recurrent bouts of
vomiting and diarrhea that typically last 24–48hours. NoVs are
transmitted via the fecal–oral route, most commonly through
infected foodor wateror person-to-person contact, and result in
267 million infections [1] and over 200,000 deaths each year,
mostlyininfantsandtheelderly[2].Vaccinesandtherapeuticsare
underdevelopmentbutfaceconsiderablechallengesasthereisno
cell-cultur
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