Dataset Information


Hepatitis C Virus Infection Activates a Novel Innate Pathway Involving IKKα in Lipogenesis and Viral Assembly

ABSTRACT: 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. 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.

ORGANISM(S): Homo sapiens  

SUBMITTER: Véronique Pène   Siddharth Krishnamurthy  Qisheng Li  T J Liang  Helen Cha  WeiPing Chen 

PROVIDER: E-GEOD-46528 | ArrayExpress | 2013-05-08



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