Vaccinia virus protein K7 is a virulence factor that alters the acute immune response to infection.
Vaccinia virus protein K7 is a virulence factor that alters the acute immune response to infection.
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DOI：
10.1099/vir.0.052670-0
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Smith GL
中科院分区：
文献类型：
--
作者：
Benfield CTO;Ren H;Lucas SJ;Bahsoun B;Smith GL
痘苗病毒 (VACV) 编码许多拮抗先天免疫系统的蛋白质，包括具有 B 细胞淋巴瘤 (Bcl)-2 样结构的细胞内蛋白质家族。其中一种名为 K7 的 Bcl-2 蛋白与 Toll 样受体适配器蛋白和 DEAD-box RNA 解旋酶 DDX3 结合，从而抑制 NF-κB 和干扰素调节因子 3 的激活。然而，K7 对病毒毒力的贡献尚不清楚。这里构建了缺乏 K7R 基因 (vΔK7) 的 VACV，并与对照病毒进行了比较，对照病毒包括噬斑纯化的 wt (vK7)、重新插入 K7R 基因的回复体 (vK7-rev) 和翻译起始密码子发生突变以阻止 K7 蛋白表达的移码病毒 (vK7-fs)。提供的数据表明，K7 的缺失不会影响细胞培养物或体内的病毒复制；然而，在小鼠皮内 (i.d.) 和鼻内 (i.n) 感染模型中，缺乏 K7 蛋白的病毒的毒性低于对照病毒，并且对感染的急性免疫反应发生了改变。在身份证中。模型中，vΔK7 诱导的病变比对照组更小，并且在注射后。感染 vΔK7 会导致体重减轻和疾病体征减少，并且病毒从受感染组织中的清除速度更快。与此同时，对 vΔK7 感染的肺内先天免疫反应显示 NK 细胞和 CD8+ T 细胞浸润增加，巨噬细胞增强 MHC II 类表达，以及 NK 细胞和 VACV 特异性 CD8+ T 细胞对靶细胞的细胞溶解增强。因此，蛋白 K7 是影响对感染的急性免疫反应的毒力因子。
Vaccinia virus (VACV) encodes many proteins that antagonize the innate immune system including a family of intracellular proteins with a B-cell lymphoma (Bcl)-2-like structure. One of these Bcl-2 proteins called K7 binds Toll-like receptor-adaptor proteins and the DEAD-box RNA helicase DDX3 and thereby inhibits the activation of NF-κB and interferon regulatory factor 3. However, the contribution of K7 to virus virulence is not known. Here a VACV lacking the K7R gene (vΔK7) was constructed and compared with control viruses that included a plaque purified wt (vK7), a revertant with the K7R gene reinserted (vK7-rev) and a frame-shifted virus in which the translational initiation codon was mutated to prevent K7 protein expression (vK7-fs). Data presented show that loss of K7 does not affect virus replication in cell culture or in vivo; however, viruses lacking the K7 protein were less virulent than controls in murine intradermal (i.d.) and intranasal (i.n.) infection models and there was an altered acute immune response to infection. In the i.d. model, vΔK7 induced smaller lesions than controls, and after i.n. infection vΔK7 induced a reduced weight loss and signs of illness, and more rapid clearance of virus from infected tissue. Concomitantly, the intrapulmonary innate immune response to infection with vΔK7 showed increased infiltration of NK cells and CD8+ T-cells, enhanced MHC class II expression by macrophages, and enhanced cytolysis of target cells by NK cells and VACV-specific CD8+ T-cells. Thus protein K7 is a virulence factor that affects the acute immune response to infection.
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影响因子：
3.7
作者：
García-Arriaza J;Nájera JL;Gómez CE;Tewabe N;Sorzano CO;Calandra T;Roger T;Esteban M
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DOI：
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发表时间：
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期刊：
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