Identification of neutralizing epitopes in the preS2 domain of the hepatitis B virus

Keigo Yato; Mami Matsuda; Kento Fukano; Tomohisa Tanaka; Kohji Moriishi; Hironori Nishitsuji; Kunitada Shimotohno; Koji Tamura; Takaji Wakita; Masamichi Muramatsu; Takanobu Kato; Ryosuke Suzuki

doi:10.1016/j.virusres.2022.199014

Identification of neutralizing epitopes in the preS2 domain of the hepatitis B virus

Virus Res. 2023 Jan 2:323:199014. doi: 10.1016/j.virusres.2022.199014. Epub 2022 Nov 26.

Authors

Affiliations

¹ Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan; Department of Biological Science and Technology, Tokyo University of Science, Tokyo, Japan.
² Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
³ Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan; Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
⁴ Department of Microbiology, Faculty of Medicine, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, Yamanashi, Japan.
⁵ Department of Microbiology, Faculty of Medicine, Graduate Faculty of Interdisciplinary Research, University of Yamanashi, Yamanashi, Japan; Division of Hepatitis Virology, Institute for Genetic Medicine, Hokkaido University, Hokkaido, Japan.
⁶ Department of Virology and Parasitology, Fujita Health University School of Medicine, Aichi, Japan.
⁷ Genome Medical Sciences Project, National Center for Global Health and Medicine, Tokyo, Japan.
⁸ Department of Biological Science and Technology, Tokyo University of Science, Tokyo, Japan.
⁹ Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan; Department of Biological Science and Technology, Tokyo University of Science, Tokyo, Japan. Electronic address: ryosuke@niid.go.jp.

Abstract

Hepatitis B virus (HBV) infection is a major public health problem. The sodium taurocholate cotransporting polypeptide (NTCP) has been identified as an essential HBV receptor. Human hepatocytes are infected with HBV via binding between the preS1 region of the HBV large envelope protein and the NTCP. However, the role of preS2 in HBV entry is not well understood. In this study, we induced anti-preS2 serum in mice by DNA immunization, and showed that the resulting antiserum neutralized HBV infectivity. Competition assays using overlapping peptides suggested that the neutralizing epitope is located in the N-terminal region of preS2. In addition, monoclonal antibodies targeting the N-terminal region of preS2 neutralized HBV infectivity, indicating that these domains are critical epitopes for viral neutralization. These findings provide new insights into the HBV entry machinery while suggesting a novel modality for the prevention and treatment of HBV infection.

Keywords: Hepatitis B virus; Neutralizing epitope; PreS2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Epitopes
Hepatitis B Surface Antigens / genetics
Hepatitis B virus* / genetics
Hepatitis B*
Humans
Mice
Viral Envelope Proteins
Virus Internalization

Substances

Epitopes
Hepatitis B Surface Antigens
Viral Envelope Proteins