Virus Expression Database
Submitted by WeiPing Chen (NIDDK NIH, USA) on Apr 30 2013
Platform: microarray – [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Pubmed: 23708292
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.
| ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
|---|---|---|---|---|---|---|
| GSM1131786 | IKK1 | hepatoma cell line  [Huh-7.5.1  ] |
48 hrs | mock | Uninfected | Extra interventions IKKalpha siRNA |
| GSM1131787 | IKK2 | hepatoma cell line [Huh-7.5.1 ] |
48 hrs | mock | Uninfected | Extra interventions IKKalpha siRNA |
| GSM1131788 | JIKK1 | hepatoma cell line [Huh-7.5.1 ] |
48 hrs | HCV JFH-1 | Hepacivirus C | Extra interventions IKKalpha siRNA |
| GSM1131789 | JIKK2 | hepatoma cell line [Huh-7.5.1 ] |
48 hrs | HCV JFH-1 | Hepacivirus C | Extra interventions IKKalpha siRNA |
| GSM1131790 | JNT1 | hepatoma cell line [Huh-7.5.1 ] |
48 hrs | HCV JFH-1 | Hepacivirus C | |
| GSM1131791 | JNT2 | hepatoma cell line [Huh-7.5.1 ] |
48 hrs | HCV JFH-1 | Hepacivirus C | |
| GSM1131792 | NT1 | hepatoma cell line [Huh-7.5.1 ] |
48 hrs | mock | Uninfected | |
| GSM1131793 | NT2 | hepatoma cell line [Huh-7.5.1 ] |
48 hrs | mock | Uninfected |