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Analysis of infection, integration and tumorigenesis of HTLV-1

HTLV-1的感染、整合和致瘤分析

基本信息

批准号：
12670272
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670272/
关键词：
HTLV-1 cell-free HTLV-1 ATL receptor integration mouse model p53

项目摘要

Human T-cell leukemia virus type 1 (HTLV-1) is an etiologic agent of adult T-cell leukemia/lymphoma and other HTLV-1-associated diseases. However, the interaction between HTLV-1 and T cells in the pathogenesis is poorly understood. We successfully infected newborn mouse with HTLV-1-producing human cells, MT-2 cells. For establishing a useful mouse model for HTLV-1 associated diseases, it is important to understand the mechanism of viral-cell interaction in mouse cells. Mouse cells have been reported to be resistant to cell-free HTLV-1 infection. However, recently we reported that HTLV-1 DNA could be observed 24 h after cell-free HTLV-1 infection to mouse cell lines as well as human cell lines. To understand HTLV-1 replication in these cells in detail, we infected mouse T cell lines, EL4 and RLm1, and human T cell line, Molt4, with the concentrated cell-free HTLV-1, produced by c77 feline kidney cell line. Unexpectedly, the amounts of adsorption and entry of HTLV-1 as measured by p19 viral protein at 4 ℃ and 37 ℃, respectively, are 3-fold and 8-fold larger in mouse cells than those in human cells. Moreover, viral DNA was detectable from 1 h in mouse cells but from 3 h in human cells. However, the amount of viral DNA in mouse cells became smaller than that in human cells. The HTLV-1 expression could be detectable until day 2 in mouse cells and until day 4 in human cells. Thus mouse cells would give useful information to dissect the early step of cell-free HTLV-1 infection, especially binding HTLV-1 to cellular receptor.

人类T细胞白血病病毒1型（HTLV-1）是成人T细胞白血病/淋巴瘤和其他HTLV-1相关疾病的病原体。然而，HTLV-1和T细胞在发病机制中的相互作用知之甚少。我们成功地用产生HTLV-1的人类细胞MT-2细胞感染新生小鼠。为了建立HTLV-1相关疾病的小鼠模型，了解小鼠细胞中病毒-细胞相互作用的机制是重要的。据报道，小鼠细胞对无细胞HTLV-1感染具有抗性。然而，最近我们报道了无细胞HTLV-1感染小鼠细胞系和人类细胞系后24小时可以观察到HTLV-1 DNA。为了详细了解HTLV-1在这些细胞中的复制，我们用c77猫肾细胞系产生的浓缩无细胞HTLV-1感染小鼠T细胞系EL 4和RLm 1以及人T细胞系Molt 4。出乎意料的是，在4 ℃和37 ℃下通过p19病毒蛋白测量的HTLV-1的吸附量和进入量在小鼠细胞中分别比在人细胞中大3倍和8倍。此外，在小鼠细胞中从1小时可检测到病毒DNA，但在人细胞中从3小时可检测到。然而，小鼠细胞中病毒DNA的量变得比人类细胞中的少。HTLV-1表达在小鼠细胞中可检测到，直到第2天，在人细胞中可检测到，直到第4天。因此，小鼠细胞将提供有用的信息，解剖无细胞HTLV-1感染的早期步骤，特别是结合HTLV-1的细胞受体。