title: Monoclonal antibody 2-152a suppresses hepatitis C virus infection through betaine/GABA transporter-1.
abstract: BACKGROUND
  We recently established a monoclonal antibody (2-152a MAb) that binds to 3β-hydroxysterol-Δ24-reductase (DHCR24) by immunizing mice with cells (RzM6-LC) persistently expressing hepatitis C virus (HCV). Here, we aimed to analyze the activity of 2-152a MAb against HCV replication and explore the molecular mechanism underlying the antiviral activity.
  
  
  METHODS
  We characterized the effects of 2-152a MAb on HCV replication and performed a microarray analysis of antibody-treated HCV replicon cells. The molecules showing a significant change after the antibody treatment were screened to examine their relationship with HCV replication.
  
  
  RESULTS
  The antibody had antiviral activity both in vitro and in vivo (chimeric mice). In the microarray analysis, 2-152a MAb significantly suppressed the expression of betaine/GABA transporter-1 (BGT-1) in 2 HCV replicon cell lines but not in HCV-cured cells. Silencing of BGT-1 expression by small interfering RNA (siRNA) revealed significant suppression of HCV replication and infection without cytotoxicity. Further, BGT-1 expression was significantly increased in the presence of HCV (P < .05).
  
  
  CONCLUSIONS
  Our results suggest that 2-152a MAb suppresses HCV replication and infection through BGT-1. These findings highlight important roles of BGT-1 in HCV replication and reveal a possible target for anti-HCV therapy.
authors.affiliation: Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, Honjo Kumamoto City, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Satoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Saito
authors.forename: Takashi
authors.initials: T
authors.lastname: Takano
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kasama
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishimura
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Nishito
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hirata
authors.forename: Masaaki
authors.initials: M
authors.lastname: Arai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sudoh
authors.forename: Chieko
authors.initials: C
authors.lastname: Kai
authors.forename: Michinori
authors.initials: M
authors.lastname: Kohara
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsukiyama-Kohara
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C072207:betaine plasma membrane transport proteins; D012313:RNA; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human