Human norovirus exhibits strain-specific sensitivity to host interferon pathways in human intestinal enteroids.
CRISPR-Cas9
RNA-Seq
enteroids/organoids
human norovirus
interferon
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
22 09 2020
22 09 2020
Historique:
pubmed:
11
9
2020
medline:
18
11
2020
entrez:
10
9
2020
Statut:
ppublish
Résumé
Human noroviruses (HuNoVs) are the leading cause of viral gastroenteritis worldwide; yet currently, no vaccines or FDA-approved antiviral drugs are available to counter these pathogens. To understand HuNoV biology and the epithelial response to infection, we performed transcriptomic analyses, RT-qPCR, CRISPR-Cas9 modification of human intestinal enteroid (HIE) cultures, and functional studies with two virus strains (a pandemic GII.4 and a bile acid-dependent GII.3 strain). We identified a predominant type III interferon (IFN)-mediated innate response to HuNoV infection. Replication of both strains is sensitive to exogenous addition of IFNs, suggesting the potential of IFNs as therapeutics. To obtain insight into IFN pathway genes that play a role in the antiviral response to HuNoVs, we developed knockout (KO) HIE lines for IFN alpha and lambda receptors and the signaling molecules,
Identifiants
pubmed: 32907944
pii: 2010834117
doi: 10.1073/pnas.2010834117
pmc: PMC7519316
doi:
Substances chimiques
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23782-23793Subventions
Organisme : NIAID NIH HHS
ID : U19 AI144297
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI116497
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056338
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201700081C
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES030285
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA125123
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007664
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI057788
Pays : United States
Déclaration de conflit d'intérêts
Competing interest statement: M.K.E. is named as an inventor on patents related to cloning and cultivation of the Norwalk virus genome and is a consultant to and received research funding from Takeda Vaccines, Inc. R.L.A. has received research funding from Takeda Vaccines, Inc.
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