Molecular mechanisms of HTLV-1 infection and pathogenesis.
Molecular mechanisms of HTLV-1 infection and pathogenesis.
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HTLV-1感染和发病机制的分子机制。
DOI：
10.1007/s12185-011-0937-1
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Yasunaga J
中科院分区：
文献类型：
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作者：
Kato S;Yamaguchi T;Ooi J;Tsukada M;Kawakita T;Tojo A;Takahashi S.;新井文子/片岡純;Aki Sato;Yasunaga J
人类 T 细胞白血病病毒 1 型 (HTLV-1) 是第一个被确定为人类癌症病原体的逆转录病毒。除了癌症、成人 T 细胞白血病 (ATL) 之外，HTLV-1 还会引起炎症性疾病，包括 HTLV-1 相关性脊髓病 (HAM)/热带痉挛性截瘫 (TSP) 和 HTLV-1 相关性葡萄膜炎 [1, 2]。 HTLV-1 通过细胞接合传播到未感染的细胞，因为无细胞病毒粒子的传播效率不高 [1]。 HTLV-1通过感染细胞的增加而不是病毒复制来增加传播机会。随后，HTLV-1 编码产物可以诱导细胞转化。除了必需的逆转录病毒成分，如长末端重复序列 (LTR)、gag、pol 和 env 之外，HTLV-1 原病毒在 env 和 30LTR 之间还有一个独特的区域；该区域被命名为 pX [3]。 pX 区域编码病毒调节和辅助蛋白 Tax、Rex、p8、p12、p13、p30、p21 和 HTLV-1 bZIP 因子 (HBZ)，这些蛋白与病毒感染性和受感染细胞的增殖有关 [3-6]。 Tax 被认为是一种有效的癌蛋白，因为它本身使人类原代 T 细胞永生化，而 Tax 转基因小鼠则形成肿瘤 [7-15]。然而，仅* 40% 的 ATL 案件中检测到了税务记录 [16, 17]。最近，病毒因子 HBZ 已被证明在体内具有致癌作用 [18]。 HBZ 的表达在所有 ATL 细胞中都是保守的，强烈表明它有助于白血病的发生。
Human T cell leukemia virus type 1 (HTLV-1) was the first retrovirus to be identified as a causative agent of a cancer in humans. In addition to cancer, adult T-cell leukemia (ATL), HTLV-1 also causes inflammatory diseases, including HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), and HTLV-1 associated uveitis [1, 2]. HTLV-1 transmits to uninfected cells through cell conjugation, as cell-free virions are not efficient in transmission [1]. HTLV-1 increases its chance of transmission by the increase of infected cells, rather than viral replication. Subsequently, HTLV-1-encoded products can induce cellular transformation. In addition to essential retroviral components, such as long terminal repeats (LTR), gag, pol and env, HTLV-1 provirus has a unique region between env and the 30LTR; and this region is named pX [3]. The pX region encodes viral regulatory and accessory proteins Tax, Rex, p8, p12, p13, p30, p21, and HTLV-1 bZIP factor (HBZ) which are implicated in viral infectivity and the proliferation of infected cells [3–6]. Tax is recognized as a potent oncoprotein, since it immortalizes human primary T cells by itself, and Tax transgenic mice form tumors [7–15]. Nevertheless, tax transcripts are detected in only* 40% of ATL cases [16, 17]. Recently, a viral factor, HBZ, has been shown to have an oncogenic effect in vivo [18]. Expression of HBZ is conserved in all ATL cells, strongly suggesting that it contributes to leukemogenesis.