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(HTLV-1)是成人T细胞白血病和HTLV-1相关性脊髓病/热带痉挛截瘫的病原体。然而，只有少数携带者在较长的潜伏期后发展为上述疾病，这给用人类材料研究其发病机制带来了困难。建立HTLV-1相关疾病的小鼠模型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。但此前已有报道称，无细胞HTLV-1不能有效感染小鼠成纤维细胞。为了了解HTLV-1对小鼠细胞的传播机制，我们利用猫肾细胞系C77产生的一株高传播性的无细胞HTLV-1，并研究了各种小鼠细胞的敏感性。感染9种小鼠细胞系EL4、RLm1、CTLL-2、J774.1、DA-1、BA/F3、WEHI-3、NIH3T3和B1，以及2种人细胞系Molt-4和Hut78，用聚合酶链式反应(PCR)检测HTLV-1前病毒序列。在所有9个小鼠细胞系和2个人细胞系中均发现HTLV-1前病毒序列，并用1名ATL患者的血清阻断感染。此外，无细胞HTLV-1感染小鼠细胞株EL4和RLm1以及人细胞株Molt-4和Hut78的效果相似。这些结果表明HTLV-1有效地无细胞传播到各种小鼠细胞系中，并表明HTLV-1受体在小鼠细胞中广泛分布。

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.