Modulation of early host innate immune response by a Fowlpox virus (FWPV) lateral body protein
Modulation of early host innate immune response by a Fowlpox virus (FWPV) lateral body protein
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DOI：
10.1101/2020.10.02.324418
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发表时间：
2020-10
期刊：
影响因子：
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通讯作者：
E. S. Giotis;S. Laidlaw;S. Bidgood;David Albrecht;J. Burden;R. Robey;J. Mercer;M. Skinner
中科院分区：
文献类型：
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作者：
E. S. Giotis;S. Laidlaw;S. Bidgood;David Albrecht;J. Burden;R. Robey;J. Mercer;M. Skinner
禽痘病毒（FWPV）是一种重要的禽痘病毒，已被成功应用于家禽和人类的疫苗接种，但其对宿主抗病毒免疫应答的调控能力却知之甚少。FWPV对禽类I型干扰素（IFN）具有高度抗性，并且能够完全阻断宿主IFN应答。在用59种不同的非必需FWPV基因敲除突变体感染的细胞中，对宿主IFN调节的基因表达进行微阵列筛选，结果显示FPV 184具有免疫调节能力。我们报道FPV 184基因敲除病毒（FWPVΔ184）最早在感染后2小时诱导细胞IFN应答。在FWPVΔ184感染的细胞中瞬时表达FPV 184可以挽救野生型、未诱导的表型。FPV 184的异位表达抑制鸡IFN-β启动子的polyI：C激活和鸡Mx启动子的IFN-α激活。共聚焦和相关的超分辨率光学和电子显微镜表明，FPV 184具有功能性核定位信号结构域，并包装在病毒粒子的侧体中。两者合计，这些结果提供了一个范例晚痘病毒结构蛋白包装在侧体，并能够抑制IFN诱导早期在下一轮感染。
The avian pathogen, fowlpox virus (FWPV) has been successfully used as vaccine vector in poultry and humans but relatively little is known about its ability to modulate host antiviral immune responses in these hosts, which are replication permissive and non-permissive, respectively. FWPV is highly resistant to avian type I interferon (IFN) and able to completely block the host IFN-response. Microarray screening of host IFN-regulated gene expression in cells infected with 59 different, non-essential FWPV gene knock-out mutants revealed that FPV184 confers immunomodulatory capacity. We report that FPV184-knockout virus (FWPVΔ184) induces the cellular IFN response as early as 2 hours post-infection. The wild-type, uninduced phenotype can be rescued by transient expression of FPV184 in FWPVΔ184-infected cells. Ectopic expression of FPV184 inhibited polyI:C activation of the chicken IFN-β promoter and IFN-α activation of the chicken Mx promoter. Confocal and correlative super-resolution light and electron microscopy demonstrated that FPV184 has a functional nuclear localisation signal domain and is packaged in the lateral bodies of the virions. Taken together, these results provide a paradigm for a late poxvirus structural protein packaged in the lateral bodies and capable of supressing IFN induction early during the next round of infection.