Giotis Efstathios S, Laidlaw Stephen M, Bidgood Susanna R, Albrecht David, Burden Jemima J, Robey Rebecca C, Mercer Jason, Skinner Michael A
Section of Virology, School of Medicine, St Mary's Campus, Imperial College, London W2 1PG, UK.
School of Life Sciences, University of Essex, Colchester C04 3SQ, UK.
Biomedicines. 2020 Dec 19;8(12):634. doi: 10.3390/biomedicines8120634.
The avian pathogen fowlpox virus (FWPV) has been successfully used as a 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 nonpermissive, 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, nonessential FWPV gene knockout mutants revealed that FPV184 confers immunomodulatory capacity. We report that the -knockout virus (FWPVΔ184) induces the cellular IFN response as early as 2 h postinfection. The wild-type, uninduced phenotype can be rescued by transient expression of in FWPVΔ184-infected cells. Ectopic expression of inhibited polyI:C activation of the chicken IFN-β promoter and IFN-α activation of the chicken Mx1 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, capable of suppressing IFN induction early during the next round of infection.
禽病原体禽痘病毒（FWPV）已成功用作家禽和人类的疫苗载体，但对于其在这些分别为病毒复制允许型和非允许型宿主中调节宿主抗病毒免疫反应的能力，人们了解得相对较少。FWPV对禽I型干扰素（IFN）具有高度抗性，并能够完全阻断宿主的IFN反应。对感染59种不同的、非必需的FWPV基因敲除突变体的细胞中宿主IFN调节基因表达进行微阵列筛选，结果显示FPV184具有免疫调节能力。我们报告称，敲除病毒（FWPVΔ184）在感染后2小时就可诱导细胞IFN反应。野生型、未诱导的表型可通过在FWPVΔ184感染的细胞中瞬时表达来挽救。的异位表达抑制了聚肌胞苷酸（polyI:C）对鸡IFN-β启动子的激活以及IFN-α对鸡Mx1启动子的激活。共聚焦以及相关的超分辨率光镜和电镜显示，FPV184具有功能性核定位信号结构域，并被包装在病毒粒子的侧体中。综上所述，这些结果为包装在侧体中的晚期痘病毒结构蛋白提供了一个范例，该蛋白能够在下一轮感染早期抑制IFN的诱导。
