In vivo tumorigenesis by Jaagsiekte sheep retrovirus (JSRV) requires Y590 in Env TM, but not full-length orfX open reading frame

In vivo tumorigenesis by Jaagsiekte sheep retrovirus (JSRV) requires Y590 in Env TM, but not full-length orfX open reading frame
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DOI:
10.1016/j.virol.2007.06.004
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发表时间:
2007-10-25
期刊:
影响因子:
3.7
通讯作者:
Fan, Hung
Fan, Hung
中科院分区:
医学3区
文献类型:
--
作者:
Cousens, Chris;Maeda, Naoyoshi;Fan, Hung

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Jaagsiekte逆转录病毒(JSRV)引起羊肺腺癌(OPA),这是绵羊的一种传染性肺癌。在体外和体内,JSRV的包膜(Env)糖蛋白是显性癌蛋白。至少在体外,JSRV Env细胞质尾部的SH2结合域(YXXM)是病毒转化的主要决定因素之一。在这些研究中,我们报道了首次在其自然宿主羊中对JSRV位点特异性突变体进行体内试验。我们发现,在体内,细胞质尾部YXXM突变为DXXM的JSRV(21)不会引起疾病,也不会引起可检测到的感染,这表明该基序列对于病毒在体内的复制和转化是绝对必需的。相比之下,JSRV开放阅读框orfX的突变没有改变JSRV诱导的疾病(21),其功能尚未确定。(c) 2007爱思唯尔公司版权所有。
Jaagsiekte retrovirus (JSRV) causes ovine pulmonary adenocarcinoma (OPA), a transmissible lung cancer of sheep. The envelope (Env) glycoprotein protein of JSRV functions as a dominant oncoprotein in vitro and in vivo. An SH2 binding domain (YXXM) in the cytoplasmic tail of the JSRV Env is one of the main determinants of viral transformation at least in vitro. In these studies, we report the first in vivo tests of site-specific mutants of JSRV in their natural host, the sheep. We show that, in vivo, JSRV(21) with the cytoplasmic tail YXXM mutated to DXXM did not cause disease nor detectable infection, indicating that this motif is absolutely required for virus replication and possibly transformation in vivo. In contrast, mutation of the JSRV open reading frame orfX, for which no function has yet been attributed, did not alter the disease induced by JSRV(21). (c) 2007 Elsevier Inc. All rights reserved.