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J Infect Dis. 2011 Oct 15;204(8):1172-80. doi: 10.1093/infdis/jir501.

Monoclonal antibody 2-152a suppresses hepatitis C virus infection through betaine/GABA transporter-1.

Author information

1
Department of Experimental Phylaxiology, Faculty of Life Sciences, Kumamoto University, Honjo Kumamoto City, Japan.

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.

PMID:
21917889
DOI:
10.1093/infdis/jir501
[Indexed for MEDLINE]

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