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

• Project/Area Number: 26870872
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology; Virology
• Research Institution: Nagasaki University
• Principal Investigator: MOI Meng Ling 長崎大学, 熱帯医学研究所, 准教授 (40597499)
• Research Collaborator: KURANE Ichiro ; TAKASAKI Tomohiko ; MORITA Kouichi
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: デング熱 / 抗体依存感染増強 / Fc gamma receptor / dengue / ADE / flavivirus / antibody / dengue hemorrhagic fever

Outline of Final 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 stably express each of the receptors. Using these cell lines, DENV infectivity was examined using conventional plaque assay and real-time PCR assay. We then determined the ADE activity to DENV using monoclonal antibodies and patient serum samples using the Fcgamma BHK cell lines. Using these monoclonal antibodies, we determined DENV infectivity in cell lines. The ADE could be detected in cell lines that express the Fcgamma IIA and IIB receptor. Overall, we have 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 Issue: 12 Pages: 810-812
  • DOI: 10.1089/vbz.2016.1982
  • Peer Reviewed / Int'l Joint Research
• [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) Issue: 1 Pages: 1-11
  • DOI: 10.1186/s12879-016-1873-8
  • NAID: 120006987630
  • 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 Issue: 1 Pages: 1-6
  • DOI: 10.1186/s41182-016-0004-y
  • NAID: 120006987654
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A first case report of Ross River virus disease patient in Japan who came back from Australia. (2014)
  • Author(s): Tochitani K, Shimizu T, Shinohara K, Tsuchido Y, Moi ML, Takasaki T.
  • Journal Title: The Journal of the Japanese Association of Infectious Diseases Volume: 88 Pages: 155-159
  • Peer Reviewed
• [Journal Article] Two cases of Zika fever imported from French Polynesia to Japan, December 2013 to January 2014. (2014)
  • Author(s): Kutsuna S, Kato Y, Takasaki T, Moi ML, Kotaki A, Uemura H, Matono T, Fujiya Y, Mawatari M, Takeshita N, Hayakawa K, Kanagawa S, Ohmagari N.
  • Journal Title: Euro Surveillence Volume: 19(4)
  • Peer Reviewed / Open Access
• [Journal Article] Determination of antibody concentration as main parameter in a dengue virus antibody-dependent enhancement assay using FcγR-expressing BHK cells. (2014)
  • Author(s): Moi ML, Takasaki T, Saijo M, Kurane I.
  • Journal Title: Archives of Virology Volume: 159(1) Pages: 103-116
  • Peer Reviewed / Open Access
• [Journal Article] Demonstration of marmosets (Callithrix jacchus) as a non-human primate model for secondary dengue virus infection: high levels of viraemia and serotype cross-reactive antibody responses consistent with secondary infection of humans. (2014)
  • Author(s): Moi ML, Takasaki T, Omatsu T, Nakamura S, Katakai Y, Ami Y, Suzaki Y, Saijo M, Akari H, Kurane I.
  • Journal Title: Journal of General Virology Volume: 95(Pt 3) Pages: 591-600
  • Peer Reviewed / Open Access
• [Journal Article] Identification and amplification of Japanese encephalitis virus and Getah virus propagated from a single porcine serum sample: A case of coinfection. (2014)
  • Author(s): Tajima S, Kotaki A, Yagasaki K, Taniwaki T, Moi ML, Nakayama E, Saijo M, Kurane I, Takasaki T.
  • Journal Title: Archives of Virology Volume: 159(11) Pages: 2969-2975
  • Peer Reviewed
• [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
• [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
• [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
  • Int'l Joint Research
• [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
• [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)
  • 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)
  • Invited
• [Presentation] Neutralizing antibody titers as a surrogate for protection against dengue: a revisit of neutralizing antibody titers of dengue virus using FcγR-expressing cells. (2014)
  • Author(s): Moi ML, Rattanamahaphoom J, Lim CK, Sirivichayakul C, Saijo M, Sabchareon A, Takasaki T, Kurane I.
  • Organizer: Joint International Tropical Meeting (JITMM)
  • Place of Presentation: Centara Grand, Central World, Bangkok, Thailand
  • Year and Date: 2014-12-02 – 2014-12-04
  • Invited
• [Presentation] デングワクチンの実用化への展望 (2014)
  • Author(s): モイメンリン
  • Organizer: 石橋記念講演
  • Place of Presentation: 東京都千代田区、学士会館
  • Year and Date: 2014-11-19
  • Invited
• [Presentation] Demonstration of common marmosets (Callithrix jacchus) as a non-human primate model for dengue vaccine development (2014)
  • Author(s): Moi ML, Shirai K, Ami Y, Miyata Y, Lim CK, Suzaki Y, Kitaura K, Saijo M, Suzuki R, Kurane I, Takasaki T.
  • Organizer: 第 62 日本ウイルス学会学術集会
  • Place of Presentation: 神奈川県横浜市、パシフィコ横浜 会議センター
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] FcγR発現細胞を用いた新規中和アッセイにて日本脳炎ワクチン接種者におけるデングウイルスに対する中和・感染増強の検討． (2014)
  • Author(s): 齋藤悠香、モイメンリン、竹下望、林昌宏、司馬肇、細野邦昭、西條政幸、倉根一郎、高崎智彦.
  • Organizer: 第 62 日本ウイルス学会学術集会
  • Place of Presentation: 神奈川県横浜市、パシフィコ横浜 会議センター
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] デング１型ウイルスの遺伝子型がヒトにおける中和・感染増強応用に及ぼす影響 (2014)
  • Author(s): 山中敦史、モイメンリン、高崎智彦、倉根一郎、小西英二.
  • Organizer: 第 62 日本ウイルス学会学術集会
  • Place of Presentation: 神奈川県横浜市、パシフィコ横浜 会議センター
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Development of a non-human primate model for primary and secondary dengue virus infection using marmosets (Callithrix jacchus). (2014)
  • Author(s): Moi ML, Shirai K, Ami Y, Lim CK, Suzaki Y, Kitaura K, Saijo M, Suzuki R, Takasaki T, Kurane I.
  • Organizer: The 63rd Annual Meeting of the American Society of Tropical Medicine and Hygiene
  • Place of Presentation: New Orleans Marriott, New Orleans, Lousiana, USA
  • Year and Date: 2014-11-02 – 2014-11-06
• [Presentation] 尿中デングウイルス非構造タンパク（NS1）抗原の ELISA 法による検出 (2014)
  • Author(s): 斎藤悠香、モイメンリン、小滝徹、池田真紀子、田島茂、司馬肇、細野邦昭、西條政幸、倉根一郎、高崎智彦
  • Organizer: 第55日本熱帯医学会大会
  • Place of Presentation: 東京都新宿区、独立行政法人国立国際医療研究センター
  • Year and Date: 2014-11-01 – 2014-11-03
• [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.
  • 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
  • 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
  • Publisher: Springer
• [Book] 帰国後診療：デング熱.実地医家のための渡航医療. 診断と治療． (2014)
  • Author(s): モイメンリン、高崎智彦
  • Publisher: 診断と治療社
• [Book] マレー渓谷脳炎ウイルス.神経症候群I (2014)
  • Author(s): モイメンリン、高崎智彦
  • Publisher: 日本臨牀社
• [Remarks]
  • URL: https://sites.google.com/site/sherrymoi/
• [Remarks] 研究者研究業績ページ
  • URL: https://sites.google.com/site/sherrymoi/
• [Remarks] 国立感染症研究所ウイルス第一部第二室研究業績ページ
  • URL: http://www0.nih.go.jp/vir1/NVL/papers_web/papers_vbv.htm