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| Status |
Public on Mar 09, 2012 |
| Title |
A Robust Induction of Type III Interferons and Chemokines Defines a Unique Pattern of Hepatic Innate Immunity in Response to Hepatitis C Virus Infection |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood. Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs, leading to IFN- stimulated gene (ISG) expression. In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways. Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs. Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders.
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| Overall design |
Samples were treated with IFN or IL28b after 6 or 24 hours with three replications
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| Contributor(s) |
Thomas E, Gonzalez VD, Li Q, Modi AA, Chen W, Noureddin M, Rotman Y, Liang TJ |
| Citation(s) |
22248663 |
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| Submission date |
Aug 03, 2011 |
| Last update date |
Mar 25, 2019 |
| Contact name |
WeiPing Chen |
| E-mail(s) |
[email protected]
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| Phone |
301-496-0175
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| Organization name |
NIDDK/NIH
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| Department |
GCL
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| Lab |
Genomics Core Lab
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| Street address |
Bldg 8, Room 1A11, NIDDK/NIH
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA144753 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE31193_RAW.tar |
245.8 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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