期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 4, 页码 E570-E579出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1615422114
关键词
enteric virus; interferon; human enteroids; human rotavirus
资金
- National Institutes of Health (NIH) [U19-AI116497, R01 AI080656, U18-TR000552, R21-AI117220]
- Howard Hughes Medical Institute [570076890]
- Advanced Technology Core Laboratories at Baylor College of Medicine
- Dan L. Duncan Cancer Center
- John S. Dunn Gulf Coast Consortium for Chemical Genomics
- Cytometry and Cell Sorting Core at Baylor College of Medicine
- Genomic and RNA Profiling Core at Baylor College of Medicine
- [P30 DK-56338]
- [P30 CA125123]
- [CPRIT RP150578]
- [P30 AI036211]
- [S10 RR024574]
- [P30 DK56338]
The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-alpha/beta) and type III IFN (IFN-lambda) function at the epithelial level, and their respective efficacies depend on the specific pathogen and site of infection. However, the roles of type I and type III IFN in restricting human enteric viruses are poorly characterized as a result of the difficulties in cultivating these viruses in vitro and directly obtaining control and infected small intestinal human tissue. We infected nontransformed human intestinal enteroid cultures from multiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNA-sequencing and functional assays. The dominant transcriptional pathway induced by HRV infection is a type III IFN-regulated response. Early after HRV infection, low levels of type III IFN protein activate IFN-stimulated genes. However, this endogenous response does not restrict HRV replication because replication-competent HRV antagonizes the type III IFN response at pre- and posttranscriptional levels. In contrast, exogenous IFN treatment restricts HRV replication, with type I IFN being more potent than type III IFN, suggesting that extraepithelial sources of type I IFN may be the critical IFN for limiting enteric virus replication in the human intestine.
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