Simian Retrovirus 4 Induces Lethal Acute Thrombocytopenia in Japanese Macaques

• DOI: 10.1128/jvi.03611-14
• Publication Date: 2015-01-22T05:59:19Z
• Authors: Rokusuke Yoshikawa; Munehiro Okamoto; Shoichi Sakaguchi; So Nakagawa; Tomoyuki Miura; Hirohisa Hirai; Takayuki Miyazawa
• Keywords: Simian immunodeficiency virus; clone (Java method); Rhesus macaque

ABSTRACT In 2001-2002, six of seven Japanese macaques ( Macaca fuscata ) died after developing hemorrhagic syndrome at the Kyoto University Primate Research Institute (KUPRI). While cause death was unknown time, we detected simian retrovirus 4 (SRV-4) in samples obtained from a similar outbreak 2008-2011, during which 42 43 exhibiting syndrome. this study, isolated SRV-4 strain PRI-172 macaque showing severe thrombocytopenia. When inoculated into four macaques, isolate induced thrombocytopenia all within 37 days. We then constructed an infectious molecular clone PRI-172, termed pSR415, and clone-derived virus two macaques. These animals also developed just 31 days inoculation, reisolated blood, bone marrow, stool. At necropsy, observed bleeding gingivae subcutaneous animals. infected variety tissues, especially digestive organs, including colon stomach, as determined by real-time reverse transcription-PCR (RT-PCR) immunohistochemical staining. Furthermore, identified receptor ASCT2, neutral amino acid transporter. ASCT2 mRNA expressed distribution proviruses correlated well with expression levels mRNA. From these results, conclude that causative agent KUPRI SRV-4, its is ASCT2. IMPORTANCE During separate outbreaks KUPRI, 2001-2002 96% (JM) died. Here, JM The molecularly cloned virus-inoculated JMs affected tissues receptor. KUPRI.