Dataset Information

IQGAP2 is a novel interferon-alpha antiviral effector gene acting non-conventionally through the NF-?B pathway.

ABSTRACT: Type I interferons (IFN) provide the first line of defense against invading pathogens but its mechanism of action is still not well understood. Using unbiased genome-wide siRNA screens, we recently identified IQ-motif containing GTPase activating protein 2 (IQGAP2), a tumor suppressor predominantly expressed in the liver, as a novel gene putatively required for IFN antiviral response against hepatitis C virus (HCV) infection. Here we sought to characterize IQGAP2 role in IFN response.We used transient small interfering RNA knockdown strategy in hepatic cell lines highly permissive to JFH1 strain of HCV infection.We found that IQGAP2 acts downstream of IFN binding to its receptor, and independently of the JAK-STAT pathway, by physically interacting with RelA (also known as p65), a subunit of the NF-?B transcription factor. Interestingly, our data reveal a mechanism distinct from the well-characterized role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-?B) in IFN production. Indeed, IFN alone was sufficient to stimulate NF-?B-dependent transcription in the absence of viral infection. Finally, both IQGAP2 and RelA were required for the induction by IFN of a subset of IFN-stimulated genes (ISG) with known antiviral properties.Our data identify a novel function for IQGAP2 in IFN antiviral response in hepatoma cells. We demonstrate the involvement of IQGAP2 in regulating ISG induction by IFN in an NF-?B-dependent manner. The IQGAP2 pathway may provide new targets for antiviral strategies in the liver, and may have a wider therapeutic implication in other disease pathogeneses driven by NF-?B activation.In this study, we identify a novel mechanism of action of interferon involving the IQGAP2 protein and the NF-?B pathway that is ultimately protective against hepatitis C virus infection. This newly identified pathway functions independently of the well-known STAT pathway and may therefore provide new targets for antiviral strategies in the liver.

SUBMITTER: Brisac C

PROVIDER: S-EPMC5656012 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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IQGAP2 is a novel interferon-alpha antiviral effector gene acting non-conventionally through the NF-κB pathway.

Brisac Cynthia C Salloum Shadi S Yang Victor V Schaefer Esperance A K EA Holmes Jacinta A JA Chevaliez Stephane S Hong Jian J Carlton-Smith Charlie C Alatrakchi Nadia N Kruger Annie A Lin Wenyu W Chung Raymond T RT

Journal of hepatology 20160709 5

<h4>Background & aims</h4>Type I interferons (IFN) provide the first line of defense against invading pathogens but its mechanism of action is still not well understood. Using unbiased genome-wide siRNA screens, we recently identified IQ-motif containing GTPase activating protein 2 (IQGAP2), a tumor suppressor predominantly expressed in the liver, as a novel gene putatively required for IFN antiviral response against hepatitis C virus (HCV) infection. Here we sought to characterize IQGAP2 role i ...[more]

PMID: 27401546

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Dataset Information

IQGAP2 is a novel interferon-alpha antiviral effector gene acting non-conventionally through the NF-?B pathway.

Publications

IQGAP2 is a novel interferon-alpha antiviral effector gene acting non-conventionally through the NF-κB pathway.

Similar Datasets

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