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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：
14570260
负责人：
MIWA Masanao
金额：
$ 2.11万
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：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570260/
关键词：
HTLV-1 mouse model viral load genetic background ATL integration insertional mutagenesis Inverse PCR セルフリーHTLV-1 レセプター

项目摘要

Previously we inoculated HTLV-1 producing cells into newborn mice and demonstrated that Human T-cell Leukemia Virus Type 1 (HTLV-1) could infect mouse. However, the process of viral proliferation and host-virus interaction is poorly understood. Recently we have succeeded in concentrating cell-free virus that retained infectious activity and established an efficient cell-free infection system. Although it was reported that HTLV-1 had low infectivity to mouse cells, we clarified HTLV-1 was able to entry into mouse cells efficiently in this system (Jap.J.Cancer Res.93 : 760-766, 2002).In human carrier, there are little data available on the factors controlling HTLV-1 proviral load. We employed a mouse model of HTLV-1 infection that we had established and found the genetic background as a determinant of HTLV-1 proviral load (Biochem.Biophys.Res.Commun.309 : 161-165, 2003).To clarify the mechanism of carcinogenesis in adult T-cell leukemia, many investigators surveyed the function of Tax protein. On the other hand, in order to investigate the possibility of insertional mutagesesis, we developed the inverse PCR and determined the precise HTLV-1 integration sites on human chromosome. Thirteen of the integration sites (52%) out of isolated 25 integration sites of HTLV-1 from 23 cases of ATL were within genes and the rate were significantly higher than that expected in the case of random integration. Interestingly, some of genes were related to the regulation of cell growth. These results did not conflict of the idea that insertional mutagenesis might contribute to the clonal selection of HTLV-1 infected cells during multistage carcinogenesis of ATL (Cancer Sci.95 : 306-310, 2004).

先前我们将HTLV-1产生细胞接种到新生小鼠体内，证实HTLV-1可以感染小鼠。然而，病毒增殖和宿主-病毒相互作用的过程尚不清楚。最近，我们成功地浓缩了无细胞病毒，保留了感染活性，并建立了一个有效的无细胞感染系统。虽然已有报道HTLV-1对小鼠细胞的感染性较低，但我们证实HTLV-1能够在该系统中有效进入小鼠细胞（jj . j .）。癌症杂志。93:760-766,2002)。在人类携带者中，关于控制HTLV-1病毒原载量的因素的资料很少。我们利用已经建立的HTLV-1感染小鼠模型，发现遗传背景是HTLV-1前病毒载量的决定因素。中国科学院学报（自然科学版）；为了阐明成人t细胞白血病的癌变机制，许多研究者对Tax蛋白的功能进行了研究。另一方面，为了研究HTLV-1基因插入突变的可能性，我们开发了反向PCR技术，确定了HTLV-1基因在人类染色体上的精确整合位点。从23例ATL中分离到的25个HTLV-1整合位点中，有13个（52%）在基因内，显著高于随机整合的预期率。有趣的是，一些基因与细胞生长的调节有关。这些结果与插入突变可能有助于HTLV-1感染细胞在ATL多阶段癌变过程中的克隆选择的观点并不冲突（Cancer Sci.95: 306- 310,2004）。