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Hepatitis C Virus Core Protein Abrogates the DDX3 Function That Enhances IPS-1-Mediated IFN-Beta Induction
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Title: | Hepatitis C Virus Core Protein Abrogates the DDX3 Function That Enhances IPS-1-Mediated IFN-Beta Induction |
Authors: | Oshiumi, Hiroyuki Browse this author | Ikeda, Masanori Browse this author | Matsumoto, Misako Browse this author →KAKEN DB | Watanabe, Ayako Browse this author | Takeuchi, Osamu Browse this author | Akira, Shizuo Browse this author | Kato, Nobuyuki Browse this author | Shimotohno, Kunitada Browse this author | Seya, Tsukasa Browse this author |
Issue Date: | 8-Dec-2010 |
Publisher: | Public Library of Science |
Journal Title: | PLoS One |
Volume: | 5 |
Issue: | 12 |
Start Page: | e14258 |
Publisher DOI: | 10.1371/journal.pone.0014258 |
Abstract: | The DEAD box helicase DDX3 assembles IPS-1 (also called Cardif, MAVS, or VISA) in non-infected human cells where minimal amounts of the RIG-I-like receptor (RLR) protein are expressed. DDX3 C-terminal regions directly bind the IPS-1 CARD-like domain as well as the N-terminal hepatitis C virus (HCV) core protein. DDX3 physically binds viral RNA to form IPS-1-containing spots, that are visible by confocal microscopy. HCV polyU/UC induced IPS-1-mediated interferon (IFN)-beta promoter activation, which was augmented by co-transfected DDX3. DDX3 spots localized near the lipid droplets (LDs) where HCV particles were generated. Here, we report that HCV core protein interferes with DDX3-enhanced IPS-1 signaling in HEK293 cells and in hepatocyte Oc cells. Unlike the DEAD box helicases RIG-I and MDA5, DDX3 was constitutively expressed and colocalized with IPS-1 around mitochondria. In hepatocytes (O cells) with the HCV replicon, however, DDX3/IPS-1-enhanced IFN-beta-induction was largely abrogated even when DDX3 was co-expressed. DDX3 spots barely merged with IPS-1, and partly assembled in the HCV core protein located near the LD in O cells, though in some O cells IPS-1 was diminished or disseminated apart from mitochondria. Expression of DDX3 in replicon-negative or core-less replicon-positive cells failed to cause complex formation or LD association. HCV core protein and DDX3 partially colocalized only in replicon-expressing cells. Since the HCV core protein has been reported to promote HCV replication through binding to DDX3, the core protein appears to switch DDX3 from an IFN-inducing mode to an HCV-replication mode. The results enable us to conclude that HCV infection is promoted by modulating the dual function of DDX3. |
Rights: | http://creativecommons.org/licenses/by/2.5/ |
Type: | article |
URI: | http://hdl.handle.net/2115/44633 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 瀬谷 司
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