Oncotarget

Research Papers: Pathology:

A novel occludin-targeting monoclonal antibody prevents hepatitis C virus infection in vitro

Ken Okai, Naoki Ichikawa-Tomikawa, Akira C. Saito, Tetsuya Watabe, Kotaro Sugimoto, Daiki Fujita, Chikako Ono, Takasuke Fukuhara, Yoshiharu Matsuura, Hiromasa Ohira and Hideki Chiba _

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Oncotarget. 2018; 9:16588-16598. https://doi.org/10.18632/oncotarget.24742

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Abstract

Ken Okai1,2,*, Naoki Ichikawa-Tomikawa1,*, Akira C. Saito1, Tetsuya Watabe1, Kotaro Sugimoto1, Daiki Fujita1, Chikako Ono3, Takasuke Fukuhara3, Yoshiharu Matsuura3, Hiromasa Ohira2 and Hideki Chiba1

1Department of Basic Pathology, Fukushima Medical University School of Medicine, Fukushima, Japan

2Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan

3Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

*These authors contributed equally to this work

Correspondence to:

Hideki Chiba, email: hidchiba@fmu.ac.jp

Keywords: tight junction; OCLN; HCV; entry factor; hepatocyte; Pathology

Received: October 27, 2017     Accepted: February 27, 2018     Published: March 30, 2018

ABSTRACT

Since hepatitis C virus (HCV) is thought to enter into host hepatocytes using the same cellular pathways regardless of the genotypes, the host factors are promising targets to prevent and treat HCV infection. Human occludin (hOCLN) is one representative entry factor, and its second extracellular loop (EC2) contributes to the species selectivity of HCV-susceptibility. However, the exact function of hOCLN during HCV entry remains unknown, and no hOCLN-targeting antibodies or synthetic drugs that prevent and treat HCV infection have yet been developed. Here we generated the anti-hOCLN-EC2 monoclonal antibody (mAb) 67-2, and demonstrated that it efficiently inhibited HCV infection in the HCV-permissive human cell line Huh7.5.1. We also showed, using three different culture systems of Huh7.5.1 cells, that this novel mAb is accessible to OCLN from the basolateral side of hepatocytes but not from the apical side. In addition, our Western blot analyses indicated that the established 67-2 mAb reacted not only with hOCLN but also with mouse OCLN, strongly suggesting that 67-2 does not recognize the human-specific amino acids in OCLN-EC2. Moreover, we revealed that the anti-hOCLN-EC2 mAb 67-2 showed no adverse effects on cell viability or the barrier function of tight junctions.


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