title: Interaction between hepatic membrane type 1 matrix metalloproteinase and acireductone dioxygenase 1 regulates hepatitis C virus infection.
abstract: Membrane type 1 matrix metalloproteinase (MT1-MMP) binds to and regulates the function of tetraspanin-enriched microdomains. It also physically interacts with claudin-1 and acireductone dioxygenase 1 (ADI1), both associated with hepatitis C virus (HCV) cell entry. Here, we examined hepatic expression of MT1-MMP, ADI1 and claudin-1 as well as their physical interaction in relation to serum or intrahepatic HCV-RNA levels. A total of 104 liver biopsies obtained from chronic hepatitis C patients and 84 liver tissues obtained from noncancerous parts of surgically removed HCV-related hepatocellular carcinoma were analysed. Positive cytoplasmic ADI1 in liver biopsies was associated with higher serum HCV-RNA levels (P = 0.009). Positive MT1-MMP and ADI1 interaction assessed by co-immunoprecipitation was associated with lower tissue HCV-RNA levels (P = 0.009). Hepatic HCV-RNA levels were positively associated with ADI1 levels in the MT1-MMP and ADI1 co-immunoprecipitates (P = 0.030). Overexpression of MT1-MMP in Huh7.5 cells suppressed cell entry of HCV pseudoparticles as well as HCVcc infection. The suppression effect could be reversed by co-expression of ADI1 in a dose-dependent manner. In summary, clinical and cell-based experiments suggested that physical interaction between MT1-MMP and ADI1 led to suppression of HCV infection. This inhibitory effect could be reversed by ADI1 overexpression.
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: M-L
authors.initials: ML
authors.lastname: Chang
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
authors.forename: J-C
authors.initials: JC
authors.lastname: Cheng
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: C-T
authors.initials: CT
authors.lastname: Yeh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002460:Cell Line; D062445:Claudin-1 / Q000032:analysis; D049308:Dioxygenases / Q000032:analysis*; D005260:Female; D019698:Hepatitis C, Chronic / Q000473:pathology* / Q000821:virology*; D022781:Hepatocytes / Q000201:enzymology / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000032:analysis*; D008875:Middle Aged; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000032:analysis*; D019562:Viral Load
chemical_list: D062445:Claudin-1; D012367:RNA, Viral; C484693:ADI1 protein, human; D049308:Dioxygenases; D053511:Matrix Metalloproteinase 14
keywords: acireductone dioxygenase 1; hepatitis C virus; membrane type-1 matrix metalloproteinase