Susceptibility of domestic animals to a pseudotype virus bearing RD-114 virus envelope protein
Susceptibility of domestic animals to a pseudotype virus bearing RD-114 virus envelope protein
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家畜对携带 RD-114 病毒包膜蛋白的假型病毒的易感性
DOI：
10.1016/j.gene.2015.04.079
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
Miyazawa Takayuki
中科院分区：
文献类型：
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作者：
Miyaho Nakaoka Rie;Nakagawa So;Hashimoto-Gotoh Akira;Nakaya Yuki;Shimode Sayumi;Sakaguchi Shoichi;Yoshikawa Rokusuke;Takahashi Ueda Mahoko;Miyazawa Takayuki
逆转录病毒载体用于基因转导到细胞中，并已应用于基因治疗。利用猫内源性逆转录病毒RD-114的包膜蛋白（Env）逆转录病毒载体进行基因转导。本研究对牛、羊、马、猪、狗、猫、雪貂、水貂、兔、大鼠、小鼠和鹌鹑等12种家畜进行了RD-114 env型病毒的易感性研究。通过比较10种哺乳动物和2种鸟类中RD-114病毒受体asct2 （SLC1A5）的核苷酸序列发现，在小鼠和大鼠谱系以及鸡和鹌鹑谱系中，RD-114病毒Env相互作用的asct2的C区插入和缺失事件独立发生。通过假型病毒感染实验，我们发现RD-114 env假型病毒能有效感染除小鼠和大鼠外的所有细胞系。此外，我们证实了牛ASCT2 （bASCT2）作为RD-114病毒感染的受体。我们还研究了bASCT2 mRNA在牛组织中的表达，发现它在肺、脾和肾等多种组织中都有表达。这些结果表明，携带RD-114 Env病毒的逆转录病毒载体可用于大型家畜以及猫、狗等伴侣动物的基因治疗。
Retroviral vectors are used for gene transduction into cells and have been applied to gene therapy. Retroviral vectors using envelope protein (Env) of RD-114 virus, a feline endogenous retrovirus, have been used for gene transduction. In this study, we investigated the susceptibility to RD-114 Env-pseudotyped virus in twelve domestic animals including cattle, sheep, horse, pig, dog, cat, ferret, mink, rabbit, rat, mouse, and quail. Comparison of nucleotide sequences ofASCT2(SLC1A5), a receptor of RD-114 virus, in 10 mammalian and 2 avian species revealed that insertion and deletion events at the region C ofASCT2where RD-114 viral Env interacts occurred independently in the mouse and rat lineage and in the chicken and quail lineage. By the pseudotype virus infection assay, we found that RD-114 Env-pseudotyped virus could efficiently infect all cell lines except those from mouse and rat. Furthermore, we confirmed that bovine ASCT2 (bASCT2) functions as a receptor for RD-114 virus infection. We also investigated bASCT2 mRNA expression in cattle tissues and found that it is expressed in various tissues including lung, spleen and kidney. These results indicate that retrovirus vectors with RD-114 virus Env can be used for gene therapy in large domestic animals in addition to companion animals such as cat and dog.