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.
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.
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.
Magot Diata
MD
Omokoko
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.
Sabar
S
Pambudi
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.
Supranee
S
Phanthanawiboon
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.
Promsin
P
Masrinoul
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.
Chayanee
C
Setthapramote
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.
Tadahiro
T
Sasaki
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.
Motoki
M
Kuhara
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.
Pongrama
P
Ramasoota
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.
Akifumi
A
Yamashita
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.
Itaru
I
Hirai
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.
Kazuyoshi
K
Ikuta
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 tkurosu@biken.osaka-u.ac.jp.
Takeshi
T
Kurosu
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D017124:Conserved Sequence; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012703:Serotyping; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D000939:Epitopes; C079340:NS1 protein, Dengue virus type 2; C546113:NS1 protein, Dengue virus type 3; C082515:NS1 protein, dengue-1 virus; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins