English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  An Image-Based Genetic Assay Identifies Genes in T1D Susceptibility Loci Controlling Cellular Antiviral Immunity in Mouse.

Liao, J., Jijon, H. B., Kim, I. R., Goel, G., Doan, A., Sokol, H., et al. (2014). An Image-Based Genetic Assay Identifies Genes in T1D Susceptibility Loci Controlling Cellular Antiviral Immunity in Mouse. PLoS One, 9(9): e108777. doi:10.1371/journal.pone.0108777.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-A847-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0026-A848-C
Genre: Journal Article

Files

show Files
hide Files
:
Liao.pdf (Publisher version), 1015KB
Name:
Liao.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2014 Liao et al
License:
-

Locators

show

Creators

show
hide
 Creators:
Liao, Juan, Author
Jijon, Humberto B., Author
Kim, Ira R., Author
Goel, Gautam, Author
Doan, Aivi, Author
Sokol, Harry, Author
Bauer, Hermann1, Author              
Herrmann, Bernhard G.1, Author              
Lassen, Kara G., Author
Xavier, Ramnik J., Author
Affiliations:
1Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              

Content

show
hide
Free keywords: -
 Abstract: The pathogenesis of complex diseases, such as type 1 diabetes (T1D), derives from interactions between host genetics and environmental factors. Previous studies have suggested that viral infection plays a significant role in initiation of T1D in genetically predisposed individuals. T1D susceptibility loci may therefore be enriched in previously uncharacterized genes functioning in antiviral defense pathways. To identify genes involved in antiviral immunity, we performed an image-based high-throughput genetic screen using short hairpin RNAs (shRNAs) against 161 genes within T1D susceptibility loci. RAW 264.7 cells transduced with shRNAs were infected with GFP-expressing herpes simplex virus type 1 (HSV-1) and fluorescent microscopy was performed to assess the viral infectivity by fluorescence reporter activity. Of the 14 candidates identified with high confidence, two candidates were selected for further investigation, Il27 and Tagap. Administration of recombinant IL-27 during viral infection was found to act synergistically with interferon gamma (IFN-γ) to activate expression of type I IFNs and proinflammatory cytokines, and to enhance the activities of interferon regulatory factor 3 (IRF3). Consistent with a role in antiviral immunity, Tagap-deficient macrophages demonstrated increased viral replication, reduced expression of proinflammatory chemokines and cytokines, and decreased production of IFN-β. Taken together, our unbiased loss-of-function genetic screen identifies genes that play a role in host antiviral immunity and delineates roles for IL-27 and Tagap in the production of antiviral cytokines.

Details

show
hide
Language(s): eng - English
 Dates: 2014-09-30
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1371/journal.pone.0108777
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: PLoS One
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 9 (9) Sequence Number: e108777 Start / End Page: - Identifier: ISSN: 1932-6203
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000277850