A novel truncated env gene isolated from a feline leukemia virus-induced thymic lymphosarcoma.
A novel truncated env gene isolated from a feline leukemia virus-induced thymic lymphosarcoma.
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从猫白血病病毒诱导的胸腺淋巴肉瘤中分离出一种新型截短的 env 基因。
DOI：
10.1128/jvi.74.3.1451-1456.2000
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发表时间：
2000
影响因子：
5.4
通讯作者：
Roy-Burman,P
中科院分区：
文献类型：
--
作者：
Shi,Y;Roy-Burman,P
我们用聚合酶链式反应从淋巴肉瘤中扩增出与猫白血病病毒(FeLV)相关的外源env基因，这些外源基因是由F6A亚群FeLV原型分子克隆F6A或新的分子克隆FeLV-A Rickard株(FRA)经皮内注射的。在检查的9个肿瘤中，6个显示在肿瘤DNA中存在大小不等的缺失环境物种。在FRA诱导的胸腺淋巴肉瘤中检测到的一个突变体，从几乎N端表面糖蛋白(SU)开始，直到环境基因跨膜(TM)蛋白的中间区域，具有较大的内部缺失。由此推导的Truncatedenv多肽(Tenv)保留了FRAenv基因N端成熟SU的完整信号肽和7个氨基酸，其次是Tm区移码的8个氨基酸。为了研究Tenv的生物学功能，我们用小鼠逆转录病毒载体产生两性病毒粒子。感染猫成纤维细胞(H927)、人纤维肉瘤细胞(HT1080)或人B淋巴瘤细胞(Raji)具有明显的细胞毒作用，而张力病毒对猫T淋巴瘤细胞(3201B)和人T淋巴瘤细胞(CEM)没有明显的细胞毒作用。综上所述，这些结果令人信服地表明，导致env基因截断的遗传事件在FeLV淋巴瘤发生了新的过程，这种产物Tenv可以对成纤维细胞和B淋巴样细胞产生细胞毒性，但对T淋巴样肿瘤细胞不产生细胞毒性。这种类型的选择性毒性可能在肿瘤疾病的发展中具有潜在的重要意义。
We PCR amplified the exogenous feline leukemia virus (FeLV)-relatedenvgene species from lymphosarcomas induced by intradermally administered plasmid DNA of either the prototype FeLV, subgroup A molecular clone, F6A, or a new molecular clone, FeLV-A, Rickard strain (FRA). Of the nine tumors examined, six showed the presence of deletedenvspecies of variable sizes in the tumor DNA. Oneenvmutant, which was detected in a FRA-induced thymic lymphosarcoma, had a large internal deletion beginning from almost the N-terminal surface glycoprotein (SU) up to the middle region of the transmembrane (TM) protein of theenvgene. The deduced polypeptide of this truncatedenv(tenv) retained the complete signal peptide and seven amino acids of the N-terminal mature SU of FRAenvgene, followed by eight amino acids from the frameshift in the TM region. To study the biological function of tenv, we used a murine retrovirus vector to produce amphotropic virions. Infection of feline fibroblasts (H927), human fibrosarcoma cells (HT1080), or human B-lymphoma cells (Raji) led to pronounced cytotoxicity, while the tenvvirus did not induce significant cytotoxicity to feline T-lymphoma cells (3201B) or human T-lymphoma cells (CEM). Together, these results convincingly demonstrated that the genetic events that led to truncation in theenvgene occurred de novo in FeLV lymphomagenesis and that such a product, tenvcould induce cytotoxicity to fibroblastic and B-lymphoid cells but not to T-lymphoid tumor cells. This type of selective toxicity might be potentially important in the development of the neoplastic disease.