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

2014 Fiscal Year Final Research Report

• 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)
• 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
• Keywords: ニホンザル / 血小板減少症 / SRV-4 / 発症機序 / 感染実験

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.

Free Research Field

分子感染症学