A new member of the interleukin 10-related cytokine family encoded by a poxvirus
A new member of the interleukin 10-related cytokine family encoded by a poxvirus
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DOI：
10.1099/vir.0.79980-0
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发表时间：
2004-06-01
影响因子：
3.8
通讯作者：
Smith, GL
中科院分区：
文献类型：
--
作者：
Bartlett, NW;Dumoutier, L;Smith, GL
痘病毒表达许多参与操纵宿主免疫应答的蛋白质。对Yaba样疾病病毒（Y134 R）的134 R蛋白的一级序列和预测结构的分析表明，它与IL-10家族的细胞蛋白，特别是IL-19、IL-20和IL-24相似。从哺乳动物细胞中表达了标记Y134 R，并鉴定为分泌的单体糖蛋白，其刺激II类细胞因子受体IL-20 R α/IL-20 R β（IL-20 R 1型）和IL-22 R/IL-20 R β（IL-20 R 2型）的信号转导。Y134 R诱导信号转导和转录激活因子的磷酸化，其易位到细胞核和报告基因表达的诱导。相反，Y134 R不能诱导来自IL-22或IFN-λ（IL-28 A、IL-2813、IL-29）II类细胞因子受体的类似应答。为了研究Y134 R在痘病毒感染期间所起的作用，构建表达Y134 R的牛痘病毒重组体并在鼠鼻内感染模型中进行测试。与对照病毒相比，表达Y134 R的病毒具有降低的毒力，表现为减少的体重减轻、疾病体征和感染器官中的病毒滴度。这些结果表明，Y134 R是IL-10相关细胞因子家族的新病毒成员，其体内活性影响病毒毒力。
Poxviruses express numerous proteins involved in manipulating the host immune response. Analysis of the primary sequence and predicted structure of the 134R protein of Yaba-like disease virus (Y134R) indicated that it is similar to cellular proteins of the IL-10 family, specifically IL-19, IL-20 and IL-24. A flag-tagged Y134R was expressed from mammalian cells and identified as a secreted, monomeric glycoprotein that stimulated signal transduction from class II cytokine receptors IL-20Ralpha/IL-20Rbeta (IL-20R type1) and IL-22R/IL-20Rbeta (IL-20R type 2). Y134R induced phosphorylation of signal transducers and activators of transcription, their translocation to the nucleus and the induction of reporter gene expression. In contrast, Y134R was unable to induce similar responses from either the IL-22 or IFN-lambda (IL-28A, IL-2813, IL-29) class II cytokine receptors. To examine the role Y134R plays during a poxvirus infection, a vaccinia virus recombinant expressing Y134R was constructed and tested in a murine intranasal infection model. Compared with control viruses, the virus expressing Y134R had a reduced virulence, manifested by reduced weight loss, signs of illness and virus titres in infected organs. These results demonstrate that Y134R is a new viral member of the IL-10-related cytokine family and that its activity in vivo affects virus virulence.