@article{81149c08d40945a3aae4d94248ab991e,
title = "A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection",
abstract = "The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III IFN (IFN-λ) 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 frommultiple individuals with human rotavirus (HRV) and assessed the host epithelial response by using RNAsequencing 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.",
keywords = "Enteric virus, Human enteroids, Human rotavirus, Interferon",
author = "Kapil Saxena and Simon, {Lukas M.} and Zeng, {Xi Lei} and Blutt, {Sarah E.} and Crawford, {Sue E.} and Sastri, {Narayan P.} and Karandikar, {Umesh C.} and Ajami, {Nadim J.} and Zachos, {Nicholas C.} and Olga Kovbasnjuk and Mark Donowitz and Conner, {Margaret E.} and Shaw, {Chad A.} and Estes, {Mary K.}",
note = "Funding Information: This work was supported by National Institutes of Health (NIH) Grants U19-AI116497 and R01 AI080656 (to M.K.E.), U18-TR000552 (to M.D.), R21-AI117220 (to M.E.C.), and Howard Hughes Medical Institute Grant 570076890 (to K.S.). This project also was supported by Advanced Technology Core Laboratories at Baylor College of Medicine. This included core support from the Integrated Microscopy Core at Baylor College of Medicine with funding from Grants P30 DK-56338 (to H. El-Serag, Principal Investigator), P30 CA125123 (to C. K. Osborne, Principal Investigator), CPRIT RP150578 (to P. Davies, Principal Investigator), the Dan L. Duncan Cancer Center and the John S. Dunn Gulf Coast Consortium for Chemical Genomics; the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the Grants P30 AI036211 (to J. Butel, Principal Investigator), P30 CA125123 (to C. K. Osborne, Principal Investigator), and S10 RR024574 (to E. Lumpkin, Principal Investigator); and the Genomic and RNA Profiling Core at Baylor College of Medicine with funding from the Grants P30 DK56338 (to H. El-Serag, Principal Investigator) and P30 CA125123 (to C. K. Osborne, Principal Investigator).",
year = "2017",
month = jan,
day = "24",
doi = "10.1073/pnas.1615422114",
language = "English (US)",
volume = "114",
pages = "E570--E579",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "4",
}