Onset and persistent mechanism of retrovirus induced thrombocytopenia in Japanese macaques.

• Project/Area Number: 24300153
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Kyoto University
• Principal Investigator: OKAMOTO Munehiro 京都大学, 霊長類研究所, 教授 (70177096)
• Co-Investigator(Kenkyū-buntansha): AKARI Hirofumi 京都大学, 霊長類研究所, 教授 (20294671) ; 鈴木 樹理 京都大学, 霊長類研究所, 准教授 (10175408)
• Co-Investigator(Renkei-kenkyūsha): ISA Tadashi 生理学研究所, 生命化学研究科, 教授 (20212805) ; SUZUKI Juri 京都大学, 霊長類研究所, 准教授 (10175408) ; MATSUOKA Masao 京都大学, ウイルス研究所, 教授 (10244138) ; MIYABE Takako 京都大学, 霊長類研究所, 助教 (10437288) ; SUZUKI Juri 京都大学, 霊長類研究所, 助教 (80418681) ; YOSHIDA Tomoyuki 京都大学, 霊長類研究所, 助教 (00451948) ; SATO Eiji 京都大学, 霊長類研究所, 助教 (90623918)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2012: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: ニホンザル / 血小板減少症 / SRV-4 / 発症機序 / 感染実験 / SRV-5 / 感染持続

Outline of Final Research Achievements

We isolated SRV-4 strain PRI-172 from a Japanese macaque showing severe thrombocytopenia. When inoculated into four Japanese macaques, the isolate induced severe thrombocytopenia in all within 37 days. We then constructed an infectious molecular clone of strain PRI-172, and inoculated the clone-derived virus into two Japanese macaques. These animals also developed severe thrombocytopenia in just 31 days after inoculation, and the virus was re-isolated from blood, bone marrow and stool. At necropsy, we observed bleeding from gingiva, and subcutaneous bleeding in all animals. SRV-4 infected various tissues especially in digestive organs including colon and stomach. We identified the SRV-4 receptor as ASCT2. ASCT2 mRNA was expressed in various tissues and the distribution of SRV-4 proviruses correlated well with the expression levels of ASCT2 mRNA. From these results, we conclude that the causative agent of hemorrhagic syndrome in Japanese macaques was SRV-4, and its receptor is ASCT2.

Research Products

• [Journal Article] Emergence of infectious malignant thrombocytopenia in Japanese macaques (Macaca fuscata) by SRV-4 after transmission to a novel host. (2015)
  • Author(s): Okamoto M, Miyazawa T, Morikawa S, Ono F, Nakamura S, Sato E, Yoshida T, Yoshikawa R, Sakai K, Mizutani T, Nagata N, Takano J, Okabayashi S, Hamano M, Fujimoto K, Nakaya T, Iida T, Horri T, Miyabe-Nishiwaki T, Watanabe A, Kaneko A, Saito A, Matsui A, Hayakawa T, Suzuki J, Akari H, Matsuzawa T, Hirai H.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 8850-8850
  • DOI: 10.1038/srep08850
  • Peer Reviewed / Open Access
• [Journal Article] Simian Retrovirus 4 Induces Lethal Acute Thrombocytopenia in Japanese Macaques. (2015)
  • Author(s): Yoshikawa Y, Okamoto M, Sakaguchi S, Nakagawa S, Miura T, Hirai H, Miyazawa T.
  • Journal Title: Journal of Virology Volume: 89 Issue: 7 Pages: 3965-3975
  • DOI: 10.1128/jvi.03611-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Construction of an infectious clone of simian foamy virus of Japanese macaque (SFVjm) and phylogenetic analyses of SFVjm isolates (2014)
  • Author(s): Yoshikawa R, Nakagawa S, Okamoto M, Miyazawa T.
  • Journal Title: Gene Volume: 548 Issue: 1 Pages: 149-154
  • DOI: 10.1016/j.gene.2014.07.025
  • Peer Reviewed
• [Journal Article] 実験動物感染症の現状「サルレトロウイスル、その後」 (2014)
  • Author(s): 岡本宗裕
  • Journal Title: 実験動物ニュース Volume: 63 Pages: 6-8
  • Peer Reviewed
• [Journal Article] Comprehensive in vitro analysis of simian retrovirus type 4 susceptibility to antiretroviral agents (2013)
  • Author(s): Tognmi, H., Shimura, K., Okamoio, M., Yoshikawa, R., MiyazHwa, T., Matsuoka M.
  • Journal Title: Journal of Virology Volume: 87 Issue: 8 Pages: 4322-4329
  • DOI: 10.1128/jvi.03208-12
  • Peer Reviewed / Open Access
• [Presentation] サルレトロウイルスによるニホンザル血小板減少症 (2014)
  • Author(s): 岡本宗裕
  • Organizer: 第124回 関西実験動物研究会
  • Place of Presentation: 京都大学 楽友会館
  • Year and Date: 2014-12-05
  • Invited
• [Presentation] Identification of a causative agent of thrombocytopenia in Japanese monkeys (Macaca fuscata) as simian retrovirus type 4. (2013)
  • Author(s): Yoshikawa, R., Okamoto, M., Miura, T., Hirai, H., and Miyazawa, T
  • Organizer: 25th Retrovirus Pathogenesis Meeting
  • Place of Presentation: Reykjavik, Iceland
• [Presentation] ニホンザル血小板減少症について (2013)
  • Author(s): 岡本宗裕
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜県、岐阜市
  • Invited
• [Presentation] ニホンザルにおけるサルレトロウイルス4型の臓器特異性の調査 (2013)
  • Author(s): 佐藤英次、鈴木樹理、渡邉朗野、兼子明久、吉川禄助、吉田友教、山中淳史、齋藤暁、齋藤波子、坂口翔一、明里宏文、宮沢孝幸、岡本宗裕
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜県、岐阜市
• [Presentation] サルレトロウイルス4型持続感染ニホンザルにおける免疫学的役割の解明 (2013)
  • Author(s): 佐藤英次、兼子明久、齋藤暁、山中淳史、鈴木樹理、渡邉朗野、吉田友教、吉川禄助、齋藤波子、牧野瀬恵美子、道家由美子、塩澤裕子、安江美雪、森本真弓、宮沢孝幸、明里宏文、岡本宗裕
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 兵庫県、神戸市
• [Presentation] 血小板減少症を呈したニホンザルからのサルレトロウイルス5型の分離と感染性クローン作成 (2012)
  • Author(s): 吉川禄助, 岡本宗裕, 宮沢孝幸
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手大学(盛岡)
  • Year and Date: 2012-09-14
• [Presentation] ニホンザル血小板減少症 (2012)
  • Author(s): 岡本宗裕
  • Organizer: 第59回日本実験動物学会
  • Place of Presentation: 別府国際コンベンションセンター(別府市)(招待講演)
  • Year and Date: 2012-05-24
• [Remarks] ニホンザル血小板減少症の原因ウイルスの特定と病態再現
  • URL: http://www.kyoto-u.ac.jp/ja/research/research_results/2014/150331_2.html