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卡波西肉瘤相关疱疹病毒K1基因对细胞生长的调控失常

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

作者信息

Lee H, Veazey R, Williams K, Li M, Guo J, Neipel F, Fleckenstein B, Lackner A, Desrosiers R C, Jung J U

机构信息

New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772-9102, USA.

出版信息

Nat Med. 1998 Apr;4(4):435-40. doi: 10.1038/nm0498-435.

Abstract

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.

摘要

在与疱疹病毒属(HVS)的赛米利里转化蛋白(STP)编码基因相当的位置,卡波西肉瘤相关疱疹病毒(KSHV)含有一个名为K1的独特开放阅读框。尽管KSHV和HVS是γ疱疹病毒亚群中相关的成员,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HVS致癌潜能所必需的,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形态学变化和集落形成,表明发生了转化。一种重组疱疹病毒,其中HVS的STP癌基因被K1取代,使原代T淋巴细胞永生化,使其能够在不依赖白细胞介素-2的情况下生长,并在普通狨猴中诱发淋巴瘤。这些结果证明了KSHV的K1基因的转化潜能。

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