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A Highly Conserved Region Between Amino Acids 221 and 266 of Dengue Virus Non-Structural Protein 1 is a Major Epitope Region in Infected Patients

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  • Department of Virology, Research Institute for Microbial Diseases (RIMD), Osaka University, Osaka, Japan; Center of Excellence for Antibody Research (CEAR), Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, Thailand; Medical and Biological Laboratories Co., Ltd., Ina, Nagano, Japan; National Institute of Infectious Diseases, Tokyo, Japan; Laboratory of Microbiology, School of Health Sciences, Faculty of Medicine, University of the Ryukyu, Okinawa, Japan
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The immune response to dengue virus (DENV) infection generates high levels of antibodies (Abs) against the DENV non-structural protein 1 (NS1), particularly in cases of secondary infection. Therefore, anti-NS1 Abs may play a role in severe dengue infections, possibly by interacting (directly or indirectly) with host factors or regulating virus production. If it does play a role, NS1 may contain epitopes that mimic those epitopes of host molecules. Previous attempts to map immunogenic regions within DENV-NS1 were undertaken using mouse monoclonal Abs (MAbs). The aim of this study was to characterize the epitope regions of nine anti-NS1 human monoclonal Abs (HuMAbs) derived from six patients secondarily infected with DENV-2. These anti-NS1 HuMAbs were cross-reactive with DENV-1, -2, and -3 but not DENV-4. All HuMAbs bound a common epitope region located between amino acids 221 and 266 of NS1. This study is the first report to map a DENV-NS1 epitope region using anti-DENV MAbs derived from patients.

Author Notes

* Address of correspondence to Takeshi Kurosu, Department of Virology, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: tkurosu@biken.osaka-u.ac.jp

Financial support: This work was supported by Grant-in-Aid for Scientific Research (C) 21790444 from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) and the Japan Science and Technology Agency (JST)/Japan International Cooperation Agency (JICA) as part of Science and Technology Research Partnership for Sustainable Development (SATREPS) Grant 08080924.

Authors' addresses: Magot Diata Omokoko, Sabar Pambudi, Supranee Phanthanawiboon, Tadahiro Sasaki, Kazuyoshi Ikuta, and Takeshi Kurosu, Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan, E-mails: omokoko@biken.osaka-u.ac.jp, sabarp@biken.osaka-u.ac.jp, supraneeoui@biken.osaka-u.ac.jp, sasatada@biken.osaka-u.ac.jp, ikuta@biken.osaka-u.ac.jp, and tkurosu@biken.osaka-u.ac.jp. Promsin Masrinoul, Institute of Molecular Biosciences, Mahidol University, Salaya, Nakhon Pathom, Thailand, E-mail: promsin.mas@mahidol.ac.th. Chayanee Setthapramote and Pongrama Ramasoota, Center of Excellence for Antibody Research (CEAR), Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Ratchathewi, Bangkok, Thailand, E-mails: lookmoo_cu@hotmail.com and pongrama.ram@mahidol.ac.th. Motoki Kuhara, Medical and Biological Laboratories Co. Ltd., Nagano, Japan, E-mail: kuhara.motoki@mbl.co.jp. Akifumi Yamashita, National Institute of Infectious Diseases, Tokyo, Japan, E-mail: uhmin@niid.go.jp. Itaru Hirai, Laboratory of Microbiology, School of Health Sciences, Faculty of Medicine, University of the Ryukyu, Okinawa, Japan, E-mail: hiraii@med.u-ryukyu.ac.jp.

Reprint requests: Takeshi Kurosu, Department of Virology, Research Institute for Microbial Diseases, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan, E-mail: tkurosu@biken.osaka-u.ac.jp.

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