 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 16, 2013 |
| Title |
Primary human hepatocytes treated with IL28B and the HCV JFH1 Genotype 2A clone. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| 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.
|
| |
|
| Overall design |
Samples were treated with JFHA, and IL28b respectively with three biological replication.
|
| |
|
| Contributor(s) |
Thomas E, Gonzalez VD, Li Q, Modi AA, Chen W, Noureddin M, Rotman Y, Liang J |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Aug 18, 2011 |
| Last update date |
Mar 25, 2019 |
| Contact name |
WeiPing Chen |
| E-mail(s) |
weipingChen@niddk.nih.gov
|
| Phone |
301-496-0175
|
| Organization name |
NIDDK/NIH
|
| Department |
GCL
|
| Lab |
Genomics Core Lab
|
| Street address |
Bldg 8, Room 1A11, NIDDK/NIH
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
|
| Samples (12)
|
|
| Relations |
| BioProject |
PRJNA145831 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE31455_RAW.tar |
219.8 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...