Translocase of outer mitochondrial membrane 70 induces interferon response and is impaired by hepatitis C virus NS3.
Hepatitis C virus (HCV) elevated expression of the translocase of outer mitochondrial membrane 70 (Tom70). Interestingly, overexpression of Tom70 induces interferon (IFN) synthesis in hepatocytes, and it was impaired by HCV. Here, we addressed the mechanism of this impairment. The HCV NS3/4A protein induced Tom70 expression. The HCV NS3 protein interacted in cells, and cleaved the adapter protein mitochondrial anti-viral signaling (MAVS). Ectopic overexpression of Tom70 could not inhibit this cleavage. As a result, IRF-3 phosphorylation was impaired and IFN-β induction was suppressed. These results indicate that MAVS works upstream of Tom70 and the cleavage of MAVS by HCV NS3 protease suppresses signaling of IFN induction.
Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo Kumamoto City, Kumamoto 860-8556, Japan.
Yuri
Y
Kasama
Makoto
M
Saito
Takashi
T
Takano
Tomohiro
T
Nishimura
Masaaki
M
Satoh
Zhongzhi
Z
Wang
Salem Nagla Elwy Salem
SN
Ali
Shinji
S
Harada
Michinori
M
Kohara
Kyoko
K
Tsukiyama-Kohara
D056945:Hep G2 Cells; D016174:Hepacivirus / Q000276:immunology / Q000472:pathogenicity*; D022781:Hepatocytes / Q000276:immunology / Q000821:virology; D006801:Humans; D057131:Immune Evasion; D007108:Immune Tolerance; D007372:Interferons / Q000037:antagonists & inhibitors / Q000276:immunology*; D033681:Mitochondrial Membrane Transport Proteins / Q000276:immunology* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000276:immunology*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D017361:Viral Nonstructural Proteins / Q000276:immunology / Q000378:metabolism*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D007372:Interferons; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C402118:TOMM70 protein, human