Experimental infection of Japanese macaques with simian retrovirus 5

Experimental infection of Japanese macaques with simian retrovirus 5
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猿猴逆转录病毒5感染日本猕猴的实验

DOI:
10.1099/jgv.0.001199
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发表时间:
2019
影响因子:
3.8
通讯作者:
Miyazawa Takayuki
Miyazawa Takayuki
中科院分区:
医学3区
文献类型:
--
作者:
Koide Rie;Yoshikawa Rokusuke;Okamoto Munehiro;Sakaguchi Shoichi;Suzuki Juri;Isa Tadashi;Nakagawa So;Sakawaki Hiromi;Miura Tomoyuki;Miyazawa Takayuki

文献摘要

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最近,在京都大学灵长类研究所(KUPRI)和国立生理科学研究所(NIPS)的外部饲养设施中,大量日本猕猴(Macaca fuscata)死于不明出血综合征。我们以前曾报道,日本猕猴在KUPRI的出血综合征是由猴逆转录病毒4(SRV-4)感染引起的,然而,在外部饲养设施发生的NIPS类似疾病的原因仍然未知。在这项研究中,我们从表现出血小板减少症的日本猕猴中分离了SRV-5,然后构建了SRV-5分离株的感染性分子克隆。当将SRV-5分离株接种到两只日本猕猴中时,在接种后22天内在两只猕猴中的一只中诱导了重度血小板减少症。类似地,将克隆衍生的病毒接种到另外两只日本猕猴中,两只猕猴中的一只在22天内出现严重的血小板减少症。另一方面,四只猕猴中的其余两只即使在给予免疫抑制剂地塞米松后仍作为无症状携带者存活。如通过实时PCR所确定的,SRV-5感染了日本猕猴的多种组织,尤其是消化和淋巴器官。我们还确定了SRV-5受体ASCT 2,日本猕猴的中性氨基酸转运蛋白。综上所述,我们得出结论,NIPS外部繁殖设施发生的出血综合征的病原体是SRV-5。
Recently, a large number of Japanese macaques (Macaca fuscata) died of an unknown hemorrhagic syndrome at Kyoto University Primate Research Institute (KUPRI) and an external breeding facility for National Institute for Physiological Sciences (NIPS). We previously reported that the hemorrhagic syndrome of Japanese macaques at KUPRI was caused by infection with simian retrovirus 4 (SRV-4); however, the cause of similar diseases that occurred at the external breeding facility for NIPS was still unknown. In this study, we isolated SRV-5 from Japanese macaques exhibiting thrombocytopenia and then constructed an infectious molecular clone of the SRV-5 isolate. When the SRV-5 isolate was inoculated into two Japanese macaques, severe thrombocytopenia was induced in one of two macaques within 22 days after inoculation. Similarly, the clone-derived virus was inoculated into the other two Japanese macaques, and one of two macaques developed severe thrombocytopenia within 22 days. On the other hand, the remaining two of four macaques survived as asymptomatic carriers even after administering an immunosuppressive agent, dexamethasone. As determined by real-time PCR, SRV-5 infected a variety of tissues in Japanese macaques, especially in digestive and lymph organs. We also identified the SRV-5 receptor as ASCT2, a neutral amino acid transporter in Japanese macaques. Taken together, we conclude that the causative agent of hemorrhagic syndrome occurred at the external breeding facility for NIPS was SRV-5.