title: Severe Fever with Thrombocytopenia Syndrome Virus Antigen Detection Using Monoclonal Antibodies to the Nucleocapsid Protein.
abstract: BACKGROUND
  Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease with a high case fatality rate, and is caused by the SFTS virus (SFTSV). SFTS is endemic to China, South Korea, and Japan. The viral RNA level in sera of patients with SFTS is known to be strongly associated with outcomes. Virological SFTS diagnosis with high sensitivity and specificity are required in disease endemic areas.
  
  
  RESULTS
  We generated novel monoclonal antibodies (MAbs) against the SFTSV nucleocapsid (N) protein and developed a sandwich antigen (Ag)-capture enzyme-linked immunosorbent assay (ELISA) for the detection of N protein of SFTSV using MAb and polyclonal antibody as capture and detection antibodies, respectively. The Ag-capture system was capable of detecting at least 350-1220 TCID50/100 μl/well from the culture supernatants of various SFTSV strains. The efficacy of the Ag-capture ELISA in SFTS diagnosis was evaluated using serum samples collected from patients suspected of having SFTS in Japan. All 24 serum samples (100%) containing high copy numbers of viral RNA (>105 copies/ml) showed a positive reaction in the Ag-capture ELISA, whereas 12 out of 15 serum samples (80%) containing low copy numbers of viral RNA (<105 copies/ml) showed a negative reaction in the Ag-capture ELISA. Among these Ag-capture ELISA-negative 12 samples, 9 (75%) were positive for IgG antibodies against SFTSV.
  
  
  CONCLUSIONS
  The newly developed Ag-capture ELISA is useful for SFTS diagnosis in acute phase patients with high levels of viremia.
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Fukuma
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Shuetsu
authors.initials: S
authors.lastname: Fukushi
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tani
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Taniguchi
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurosu
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Egawa
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Suda
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Harpal
authors.initials: H
authors.lastname: Singh
authors.affiliation: Miyazaki Prefectural Institute for Public Health and Environment, Miyazaki, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Nomachi
authors.affiliation: Kagoshima Prefectural Institute for Environmental Research and Public Health, Kagoshima, Japan.
authors.forename: Mutsuyo
authors.initials: M
authors.lastname: Gokuden
authors.affiliation: Saga Prefectural Institute of Public Health and Pharmaceutical Research, Saga, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ando
authors.affiliation: Okayama Prefectural Institute for Public Health and Environmental Science, Okayama, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kida
authors.affiliation: Ehime Prefectural Institute of Public Health and Environmental Science, Ehime, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kan
authors.affiliation: Health and Sanitation Office, Tottori Prefecture Institute of Public Health and Environmental Science, Tottori, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kato
authors.affiliation: Nagasaki Prefectural Institute for Environmental Research and Public Health, Public Health Science Research Center, Nagasaki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshikawa
authors.affiliation: Hyogo Prefectural Institute of Public Health and Consumer Sciences, Hyogo-ku Kobe-shi, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kitamoto
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Tadaki
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morikawa
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shimojima
authors.affiliation: Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saijo
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000097:blood*; D002044:Bunyaviridae Infections / Q000175:diagnosis*; D003955:Diagnostic Tests, Routine / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D019590:Nucleocapsid Proteins / Q000097:blood*; D016856:Phlebovirus / Q000302:isolation & purification*; D012680:Sensitivity and Specificity; D012698:Serologic Tests / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D019590:Nucleocapsid Proteins