Norovirus-induced immune response in human intestinal enteroids
Refereed conference paper presented and published in conference proceedings

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AbstractIntroduction. Norovirus is the leading cause of acute gastroenteritis. The pathogenesis of norovirus and the induced immune response remain poorly understood due to the lack of a robust virus culture system.

Aims. We investigated the profile of immune response in the recently developed human intestinal enteroid (HIE) model upon norovirus infection to evaluate its clinical relevance in natural infections.

Methods. We challenged two secretor positive HIE lines with two norovirus pandemic GII.Pe-GII.4 Sydney strains at a multiplicity of infection of 50. The viral load of supernatants and cell lysates at 1, 24 and 72 hours post inoculation (hpi) were quantified by RT-qPCR. Immune gene RNA expression levels were profiled using RT2 PCR array of the “Innate and Adaptive” pathway and the “Human Interferon and Receptors” pathways. Secreted protein level of shortlisted up-regulated genes was measured in supernatants using analyte-specific ELISA.

Results. Productive norovirus replications were achieved in three (75%) out of four inoculations, with a maximum RNA fold increase of 51 and 154 at 72 hpi in supernatant and cell lysate, respectively. CXCL10 and IFI44L were the most up-regulated gene, with 93 and 580 folds in the “Innate and Adaptive” and “Human Interferon and Receptors” pathway, respectively. Gene expression of CXCL10 and IFI44L is positively correlated with the level of norovirus replication (CXCL10: Spearman’s r=0.779, p<0.05; IFI44L: r=0.881, p<0.01). The higher level of secreted protein confirmed elevated gene expression.

Discussion. Elevated CXCL10 level has been reported in blood of norovirus gastroenteritis patients. Moreover, IFI44L is up-regulated in many acute viral infections and is a biomarker to distinguish between viral and bacterial infections. These data suggested that HIE could mimic the innate immune response elicited in natural norovirus infection without co-culturing with immune cells, and therefore could serve as an experimental model for future virus-host interaction and antiviral studies (GRF-14162217).
All Author(s) ListChan J, Mohammad K, Zhang L, Wong S, Chan M
Name of ConferenceThe 7th International Calicivirus Conference
Start Date of Conference13/10/2019
End Date of Conference17/10/2019
Place of ConferenceSydney
Country/Region of ConferenceAustralia
Proceedings TitleScientific Program of the 7th International Calicivirus Conference
LanguagesEnglish-United States
Keywordsnorovirus, enteroids

Last updated on 2020-26-05 at 15:15