Free Transmission of Human T-cell Leukemia Virus Type 1 to Mouse Cells

人类 T 细胞白血病病毒 1 型向小鼠细胞的自由传播

基本信息

批准号：
10670280
负责人：
MIWA Masanao
金额：
$ 2.05万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670280/
关键词：
Human Retrovirus HTLV-1 ATL Animal model Mouse Leukemia

项目摘要

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent for adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, the fact that only a few carriers develop to the above diseases after a long latency makes it difficult to study their pathogenesis with human material. It would be helpful to establish a mouse model of HTLV-1-associated diseases to understand their pathogenesis. Recently we could infect newborn mice by inoculating HTLV-1-producing human cells. We found that T-cells, B-cells and granulocytes were infected in vivo. But it has been previously reported that cell-free HTLV-1 could not infect mouse fibroblast cells efficiently. To understand the mechanism of HTLV-1 transmission to mouse cells, we employed a highly transmissible cell-free HTLV-1 produced by a feline kidney cell line, c77 and studied the susceptibility of various kinds of mouse cells. Nine kinds of mouse cell lines, EL4, RLm1, CTLL-2, J774.1, DA-1, Ba/F3, WEHI-3, NIH3T3 and B1, and two kinds of human cell lines, Molt-4 and Hut78, were infected and the HTLV-1 provirus sequence was monitored by PCR. HTLV-1 proviral sequence was found in all 9 mouse cell lines as well as in 2 human cell lines and infection was blocked with serum from an ATL patient. Moreover mouse cell lines, EL4 and RLm1, and human cell lines, Molt-4 and Hut78, were infected by cell-free HTLV-1 with similar efficiency. These results indicate efficient cell-free HTLV-1 transmission to various mouse cell lines and suggest a wide distribution of HTLV-1 receptor in mouse cells.

人类 T 细胞白血病病毒 1 型 (HTLV-1) 是成人 T 细胞白血病和 HTLV-1 相关脊髓病/热带痉挛性截瘫的病原体。然而，只有少数携带者在长时间潜伏期后发展为上述疾病，这使得用人体材料研究其发病机制变得困难。建立HTLV-1相关疾病的小鼠模型将有助于了解其发病机制。最近，我们可以通过接种产生 HTLV-1 的人类细胞来感染新生小鼠。我们发现T细胞、B细胞和粒细胞在体内被感染。但此前有报道称，无细胞HTLV-1不能有效感染小鼠成纤维细胞。为了了解HTLV-1向小鼠细胞传播的机制，我们采用了猫肾细胞系c77产生的高传播性无细胞HTLV-1，并研究了各种小鼠细胞的敏感性。检测了 EL4、RLm1、CTLL-2、J774.1、DA-1、Ba/F3、WEHI-3、NIH3T3 和 B1 9 种小鼠细胞系以及 Molt-4 和 Hut78 2 种人细胞系。感染并通过 PCR 监测 HTLV-1 原病毒序列。在所有 9 种小鼠细胞系以及 2 种人类细胞系中均发现了 HTLV-1 前病毒序列，并且用来自 ATL 患者的血清阻断了感染。此外，小鼠细胞系 EL4 和 RLm1 以及人类细胞系 Molt-4 和 Hut78 被无细胞 HTLV-1 感染的效率相似。这些结果表明 HTLV-1 能够有效地无细胞传输至各种小鼠细胞系，并表明 HTLV-1 受体在小鼠细胞中广泛分布。