Determination of the role of Fcgamma receptor in antibody-dependent enhancement of dengue virus infection

2016 Fiscal Year Annual Research Report

• Project/Area Number: 26870872
• Research Institution: Nagasaki University
• Principal Investigator: モイ メンリン 長崎大学, 熱帯医学研究所, 准教授 (40597499)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: dengue / ADE / flavivirus

Outline of Annual Research Achievements

In this research we aim to determine the role of Fcgamma receptor in infection-enhancement (ADE) of dengue virus (DENV). Here, we have constructed the plasmids of Fcgamma receptors (I, IIA, IIB, III), and expressed the plasmids into DENV-permissive cells, to establish cell lines that express each of the receptors. Using these cell lines, DENV infectivity was examined by using conventional plaque assay and real-time PCR assay. We then determined the ADE activity to DENV by using monoclonal antibodies, dengue patient and Japanese encephalitis (JE) vacinee serum samples using the Fcgamma BHK cell lines. We also demonstrated the utility of the Fcgamma receptor expressing cell lines in determining the ADE levels of antibodies in dengue patients and an animal model. Using monoclonal antibodies that demonstrated ADE activity, we determined DENV infectivity in each of the Fcgamma receptor expressing cell lines. ADE activity was detected by using cell lines that express the Fcgamma IIA and IIB receptors, confirming that these receptors are important in ADE of flavivirus infection. Overall, we established Fcgamma receptor expressing cell lines that are useful in DENV diagnosis and pathogenesis studies.

Research Products

• [Journal Article] Dengue Virus Isolation in Mosquito Aedes albopictus Captured During an Outbreak in Tokyo, 2014, by a Method Relying on Antibody-Dependent Enhancement Mechanism Using FcγR-Expressing BHK Cells. (2016)
  • Author(s): Moi ML, Kobayashi D, Isawa H, Sasaki T, Saijo M, Kurane I, Sawabe K, Takasaki T.
  • Journal Title: Vector Borne Zoonotic Dis. Volume: 16(1) Pages: 810-812
  • DOI: 10.1089/vbz.2016.1982
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Japanese encephalitis vaccine-facilitated dengue virus infection-enhancement antibody in adults. (2016)
  • Author(s): Saito Y, Moi ML, Takeshita N, Lim CK, Shiba H, Hosono K, Saijo M, Kurane I, Takasaki T.
  • Journal Title: BMC Infect Dis. Volume: 16(12) Pages: 1-11
  • DOI: 10.1186/s12879-016-1873-8
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Human antibody response to dengue virus: implications for dengue vaccine design (2016)
  • Author(s): Moi ML, Takasaki T, Kurane I.
  • Journal Title: Trop Med Health. Volume: 44(1):578 Pages: 1-6
  • DOI: 10.1186/s41182-016-0004-y
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Common marmosets as non-human primate model for dengue vaccine development: demonstration of protective immunity after vaccination. (2016)
  • Author(s): Moi ML, Sutee Yoksan, Ami Y, Shirai K, Azami NAM, Saito Y, Suzaki Y, Kitaura K, Saijo M, Suzuki R, Takasaki T, Kurane I.
  • Organizer: 第 64 日本ウイルス学会学術集会.
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] Determination of dengue virus (DENV) serotype and genotype specific neutralizing antibodies during secondary virus infection in marmosets. (2016)
  • Author(s): Azami NAM, Moi ML, Ami Y, Suzaki Y, Saijo M, Takasaki T, Kurane I.
  • Organizer: 第 64 日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2016-10-23 – 2016-10-25
• [Presentation] Dengue viremia and immune response in adults during the early phase of primary infection. (2016)
  • Author(s): Moi ML, Saito Y, Kotaki A, Tajima S, Saijo M, Kurane T.
  • Organizer: 第11回日中ウイルス国際学会
  • Place of Presentation: 琴弾荘（香川県・観音寺市）
  • Year and Date: 2016-07-01 – 2016-07-02
  • Int'l Joint Research
• [Presentation] Recent advances in Zika virus research. (2016)
  • Author(s): Moi ML
  • Organizer: San Lazaro Hospital, St Lukes Medical Center, invited lecture
  • Place of Presentation: St Lukes Medical Center (Manila, Philippines)
  • Year and Date: 2016-06-20 – 2016-06-20
  • Invited
• [Presentation] Recent advances in Zika virus diagnosis (2016)
  • Author(s): Moi ML
  • Organizer: Universiti Kebangsaan Malaysia, Institute of Molecular Biology (UMBI), invited lecture
  • Place of Presentation: Universiti Kebangsaan Malaysia, Institute of Molecular Biology, UMBI (Kuala Lumpur, Malaysia)
  • Year and Date: 2016-04-25 – 2016-04-25
  • Invited
• [Presentation] Development of an efficient dengue virus (DENV) isolation assay using an antibody-dependent (ADE) mechanism by FcgR-expressing cells (2016)
  • Author(s): Moi ML, Takasaki T, Azila NAM, Saijo M, Kurane I.
  • Organizer: Asia Dengue Conference
  • Place of Presentation: Marriott Hotel (Kuala Lumpur, Malaysia)
  • Year and Date: 2016-04-23 – 2016-04-24
• [Book] Hemorrhagic Fever Viruses - Methods and Protocols: Detection of virus-antibody immune complexes in secondary dengue virus infection (2017)
  • Author(s): Moi ML, Takasaki T, Kurane I.
  • Total Pages: in press
  • Publisher: Springer
• [Book] Methods Mol Biol. Chikungunya Virus Growth and Fluorescent Labeling: Detection of Chikungunya Virus by Immunofluorescence Assay. (2016)
  • Author(s): Moi ML, Takasaki T
  • Total Pages: 143-152
  • Publisher: Springer
• [Book] Methods Mol Biol. Neutralization Assay for Chikungunya Virus Infection: Plaque Reduction Neutralization Test. (2016)
  • Author(s): Azami NA, Moi ML, Takasaki T
  • Total Pages: 273-282
  • Publisher: Springer
• [Remarks]
  • URL: https://sites.google.com/site/sherrymoi/