Yasunaga Jun-ichirou, Matsuoka Masao
Laboratory of Human Tumor Viruses Department of Viral Oncology Institute for Virus Research, Kyoto University.
Uirusu. 2006 Dec;56(2):241-9. doi: 10.2222/jsv.56.241.
Human T-cell leukemia virus type I (HTLV-I) is a causative virus of adult T-cell leukemia (ATL). ATL is a highly aggressive neoplastic disease of CD4 positive T lymphocyte, which is featured by the pleomorphic tumor cells with hypersegmented nuclei, called " flower cell". HTLV-I increases its copy number by clonal proliferation of the host cells, not by replication of the virus. Therefore, HTLV-I eventually induces ATL. Tax, encoded by HTLV-I pX region, has been recognized as a protein that plays a central role of the transformation of HTLV-I-infected cells by its pleiotropic actions. However, fresh ATL cells frequently lose Tax protein expression by several mechanisms. Recently, HBZ was identified in the complementary strand of HTLV-I and it is suggested that HBZ is a critical gene in leukemogenesis. Furthermore, there is a long latency period before onset of ATL, indicating the multistep mechanisms of leukemogenesis. Therefore, it is suggested that multiple factors, such as viral proteins, genetic and epigenetic changes of host genome, and immune status of the hosts, could be implicated in leukemogenesis of ATL.
人类嗜T淋巴细胞病毒I型（HTLV-I）是成人T细胞白血病（ATL）的致病病毒。ATL是一种CD4阳性T淋巴细胞的高度侵袭性肿瘤疾病，其特征是具有细胞核高度分叶的多形性肿瘤细胞，称为“花细胞”。HTLV-I通过宿主细胞的克隆增殖而非病毒复制来增加其拷贝数。因此，HTLV-I最终诱发ATL。由HTLV-I pX区域编码的Tax蛋白，因其多效性作用而被认为是在HTLV-I感染细胞转化过程中起核心作用的蛋白。然而，新鲜的ATL细胞常通过多种机制丧失Tax蛋白表达。最近，在HTLV-I的互补链中鉴定出HBZ，提示HBZ是白血病发生中的关键基因。此外，ATL发病前有很长的潜伏期，表明白血病发生存在多步骤机制。因此，提示病毒蛋白、宿主基因组的遗传和表观遗传变化以及宿主的免疫状态等多种因素可能与ATL的白血病发生有关。
