title: Hepatitis C virus suppresses C9 complement synthesis and impairs membrane attack complex function.
abstract: Hepatitis C virus (HCV) proteins inhibit complement component expression, which may attenuate immunity against infection. In this study, we examined whether HCV regulates the membrane attack complex (MAC) via complement component C9. MAC is composed of C5b to C9 (C5b-9) and mediates cell lysis of invaded pathogens. Liver biopsy specimens from chronically HCV-infected patients exhibited a lower level of C9 mRNA expression than liver biopsy specimens from unrelated disease or healthy control human liver RNA. Hepatocytes infected with cell culture-grown HCV or expressing HCV core protein also displayed significant repression of C9 mRNA and protein levels. Promoter analysis suggested that the T cell factor-4 (TCF-4E) transcription factor is responsible for HCV core-mediated C9 promoter regulation. Sera from chronically HCV-infected patients displayed a lower level of C5b-9 and a reduced antimicrobial effect on model organisms compared to unrelated patient sera or sera from healthy volunteers. Together, these results for C9 regulation by HCV core protein coupled with functional impairment of the membrane attack complex underscore HCV-mediated attenuation of immune mechanisms.
authors.affiliation: Department of Internal Medicine, Saint Louis University, St Louis, Missouri, USA.
authors.forename: Hangeun
authors.initials: H
authors.lastname: Kim
authors.forename: Keith
authors.initials: K
authors.lastname: Meyer
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ray
mesh_terms: D001706:Biopsy; D003186:Complement C9 / Q000037:antagonists & inhibitors*; D015938:Complement Membrane Attack Complex / Q000037:antagonists & inhibitors*; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000276:immunology* / Q000472:pathogenicity*; D019698:Hepatitis C, Chronic / Q000473:pathology; D006801:Humans; D057131:Immune Evasion; D008099:Liver / Q000473:pathology
chemical_list: D003186:Complement C9; D015938:Complement Membrane Attack Complex