Deregulation of cell growth by the K1 gene of Kaposi's sarcoma-associated herpesvirus

Deregulation of cell growth by the K1 gene of Kaposi's sarcoma-associated herpesvirus
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DOI:
10.1038/nm0498-435
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发表时间:
1998-04-01
期刊:
影响因子:
82.9
通讯作者:
Jung, JU
Jung, JU
中科院分区:
医学1区
文献类型:
--
作者:
Lee, H;Veazey, R;Jung, JU

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卡波西肉瘤相关疱疹病毒(KSHV)在与编码松鼠猴疱疹病毒(HVS)的松鼠猴转化蛋白(STP)的基因相当的位置含有一个独特的开放阅读框,称为K1。虽然KSHV和HVS是γ疱疹病毒的鼻病毒亚组的相关成员,但K1和STP在氨基酸序列或结构组织上没有相似性。由于STP是所需的HVS的致癌潜力,我们研究了K1表达的功能后果。K1基因在啮齿动物成纤维细胞中的表达产生了指示转化的形态学变化和焦点形成。将HVS的STP癌基因替换为K1的重组疱疹病毒,使原代T淋巴细胞永生化,使其不依赖于IL-2生长,并在普通绒猴中诱导淋巴瘤。这些结果表明KSHV的K1基因的转化潜力。
At a position equivalent to the gene encoding the saimiri transforming protein (STP) of herpesvirus saimiri (HVS), Kaposi's sarcoma-associated herpesvirus (KSHV) contains a distinct open reading frame called K1. Although KSHV and HVS are related members of the rhadinovirus subgroup of gamma herpesviruses, K1 and STP exhibit no similarity in amino acid sequence or in structural organization. Since STP is required for the oncogenic potential of HVS, we investigated the functional consequence of K1 expression. Expression of the K1 gene in rodent fibroblasts produced morphologic changes and focus formation indicative of transformation. A recombinant herpesvirus in which the STP oncogene of HVS was replaced with K1, immortalized primary T lymphocytes to IL-2 independent growth and induced lymphoma in common marmosets. These results demonstrate the transforming potential of the K1 gene of KSHV.