Monoclonal Antibody 2-152a Suppresses Hepatitis C Virus Infection Through Betaine/GABA Transporter-1

Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, Honjo Kumamoto City, Japan.
The Journal of Infectious Diseases (Impact Factor: 6). 10/2011; 204(8):1172-80. DOI: 10.1093/infdis/jir501
Source: PubMed


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.
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.
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).
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.

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    • "Recently, we found that silencing of DHCR24 by siRNA suppresses HCV replication [39] and an inhibitor of DHCR24 (U18666A) had an anti-viral effect in vivo. Monoclonal antibodies to DHCR24 (2-152a) suppress HCV replication through the betaine GABA transporter-1 (BGT-1) [40]. Thus, DHCR24 is involved in HCV replication and pathogenicity. "
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