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| Status |
Public on May 08, 2013 |
| Title |
Hepatitis C Virus Infection Activates a Novel Innate Pathway Involving IKKα in Lipogenesis and Viral Assembly |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Hepatitis C virus interacts extensively with host factors not only to establish productive infection but also to trigger unique pathological processes. Our recent genome-wide siRNA screen demonstrated that IKKα is a critical host factor for HCV. Here we describe a novel NF-κB-independent and kinase-mediated nuclear function of IKKα in HCV assembly. HCV infection, through its 3’-untranslated region, interacts with DDX3X to activate IKKα, which translocates to the nucleus and induces a CBP/p300-mediated transcriptional program involving SREBPs. This novel innate pathway induces lipogenic genes and enhances core-associated lipid droplet formation to facilitate viral assembly. Chemical inhibitors of IKKα suppress HCV infection and IKKα-induced lipogenesis, offering a proof-of-concept approach for novel HCV therapeutic development. Our results show that HCV commands a novel mechanism to its advantage by exploiting intrinsic innate response and hijacking lipid metabolism, which likely contributes to a high chronicity rate and the pathological hallmark of steatosis in HCV infection.
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| Overall design |
Cells were treated with either non-targeting control siRNA or siRNA against IKKalpha. After 72 h, cells were either mock infected or infected with HCV JFH-1 strain with the M.O.I. of 0.5.
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| Contributor(s) |
Li Q, Cha H, Pène V, Liang TJ, Krishnamurthy S |
| Citation(s) |
23708292 |
| |
| Submission date |
Apr 30, 2013 |
| Last update date |
Mar 25, 2019 |
| Contact name |
WeiPing Chen |
| E-mail(s) |
weipingChen@niddk.nih.gov
|
| Phone |
301-496-0175
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| 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 |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA201062 |
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