TY - JOUR
T1 - Identification of neutralizing epitopes in the preS2 domain of the hepatitis B virus
AU - Yato, Keigo
AU - Matsuda, Mami
AU - Fukano, Kento
AU - Tanaka, Tomohisa
AU - Moriishi, Kohji
AU - Nishitsuji, Hironori
AU - Shimotohno, Kunitada
AU - Tamura, Koji
AU - Wakita, Takaji
AU - Muramatsu, Masamichi
AU - Kato, Takanobu
AU - Suzuki, Ryosuke
N1 - Funding Information:
The authors of this manuscript express their gratitude to N. Nishiyama for technical assistance, and to Y. Hirama for administrative assistance. The GroEL-encoding plasmid was kindly provided by Dr. J. Chiba (Tokyo University of Science). This research was supported by the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP19fk0310120 , JP22fk0210109 and JP22fk0310503 .
Funding Information:
The authors of this manuscript express their gratitude to N. Nishiyama for technical assistance, and to Y. Hirama for administrative assistance. The GroEL-encoding plasmid was kindly provided by Dr. J. Chiba (Tokyo University of Science). This research was supported by the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP19fk0310120, JP22fk0210109 and JP22fk0310503.
Publisher Copyright:
© 2022 The Author(s)
PY - 2023/1/2
Y1 - 2023/1/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.virusres.2022.199014
DO - 10.1016/j.virusres.2022.199014
M3 - Article
C2 - 36511290
AN - SCOPUS:85143515741
VL - 323
JO - Virus Research
JF - Virus Research
SN - 0168-1702
M1 - 199014
ER -