Differences in interferon sensitivity and biological properties of two related isolates of simian virus 5: A model for virus persistence
Differences in interferon sensitivity and biological properties of two related isolates of simian virus 5: A model for virus persistence
复制标题
DOI：
10.1006/viro.2001.1302
复制
发表时间：
2002-02-15
期刊：
影响因子：
3.7
通讯作者：
Randall, RE
中科院分区：
文献类型：
--
作者：
Chatziandreou, N;Young, D;Randall, RE
CP1(+)和CP1(-)是猿猴病毒5(SV5)的两种犬分离株。 CPl(+)最初从患有暂时性后麻痹的狗的脑脊液中分离出来，CPl(-)在注射后第12天回收。来自实验性感染 CPl(+) 的狗的脑组织。我们之前已经证明，SV5 的 V 蛋白通过靶向 STAT1 降解来阻断干扰素 (IFN) 信号传导。在这里，我们报道，虽然CPl(+)靶向STAT1进行降解，但CPl(-)未能，因此，CPl(+)阻断IFN信号传导，但CPl(-)不会。 V蛋白的P/V N端共同结构域中的三个氨基酸差异是观察到的CP1(+)和CP1-阻断IFN信号转导的能力差异的原因。在持续感染CPl(-)的细胞中，病毒可能响应IFN而受到抑制，在这种情况下，病毒糖蛋白从被感染细胞的表面丢失，病毒核衣壳蛋白在细胞质包涵体中积累。我们认为体内感染IFN抗性病毒的细胞（其中将有持续的病毒蛋白合成）可能比感染IFN敏感病毒的细胞（其中病毒蛋白合成被抑制）更容易被细胞毒性T细胞杀死，并且提出了病毒持久性模型，其中根据适应性免疫反应的状态交替选择抗干扰素和干扰素敏感病毒。 (C) 2002 年爱思唯尔科学（美国）。
CPl(+) and CPl(-) are two canine isolates of simian virus 5 (SV5). CPl(+) was originally isolated from the cerebrospinal fluid of a dog with temporary posterior paralysis and CPl(-) was recovered at 12 days p.i. from the brain tissue of a dog experimentally infected with CPl(+). We have previously shown that the V protein of SV5 blocks interferon (IFN) signalling by targeting STAT1 for degradation. Here we report that whilst CPl(+) targets STAT1 for degradation, CPl(-) fails to and as a consequence, CPl(+) blocks IFN signalling but CPl(-) does not. Three amino acid differences in the P/V N-terminal common domain of the V protein are responsible for the observed difference in the abilities of CPl(+) and CPl- to block IFN signalling. In cells persistently infected with CPl(-) the virus may become repressed in response to IFN, under which circumstances virus glycoproteins are lost from the surface of infected cells and virus nucleocapsid proteins accumulate in cytoplasmic inclusion bodies, We suggest that in vivo cells infected with IFN-resistant viruses (in which there would be continuous virus protein synthesis) may be more susceptible to killing by cytotoxic T cells than cells infected with IFN-sensitive viruses (in which virus protein synthesis was repressed), and a model of virus persistence is put forward in which there is alternating selection of IFN-resistant and IFN-sensitive viruses depending upon the state of the adaptive immune response. (C) 2002 Elsevier Science (USA).