National Microbiology Laboratory, The Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba, R3E 3R2, Canada; Department of Medical Microbiology, University of Manitoba, 543-745 Bannatyne Avenue, Winnipeg, Manitoba, R3E 0J9, Canada.
National Microbiology Laboratory, The Public Health Agency of Canada, 1015 Arlington Street, Winnipeg, Manitoba, R3E 3R2, Canada.
Virology. 2020 Feb;541:101-112. doi: 10.1016/j.virol.2019.12.008. Epub 2019 Dec 23.
Protein kinase R plays a key role in innate antiviral immune responses of vertebrate animals. Most mammalian poxviruses encode two PKR antagonists, E3 (dsRNA binding) and K3 (eIF2α homolog) proteins. In this study, the role of K3 family proteins from poxviruses with distinct host tropisms in determining the virus host range was examined in a vaccinia E3L deletion mutant virus. It was found that K3 orthologs from the species-specific poxviruses (taterapox virus, sheeppox virus, myxoma virus, swinepox virus and yaba monkey tumor virus) restored the virus replication competency in cells derived from their natural hosts or related animal species. Further, it was found that the residues located in the helix insert region of the protein, K45 of vaccinia K3 and Y47 of the sheep poxvirus ortholog 011, are critical for the virus host species specificity. These observations demonstrate that poxvirus K3 proteins are major determinants of the virus host specificity.
蛋白激酶 R 在脊椎动物的先天抗病毒免疫反应中发挥关键作用。大多数哺乳动物痘病毒编码两种 PKR 拮抗剂，E3（dsRNA 结合）和 K3（eIF2α 同源物）蛋白。在这项研究中，研究了具有不同宿主趋向性的痘病毒 K3 家族蛋白在确定病毒宿主范围中的作用，使用的是痘苗病毒 E3L 缺失突变病毒。研究发现，来自种特异性痘病毒（牛痘病毒、绵羊痘病毒、兔痘病毒、猪痘病毒和雅巴猴肿瘤病毒）的 K3 同源物恢复了源自其自然宿主或相关动物物种的细胞中的病毒复制能力。此外，还发现位于蛋白质螺旋插入区的残基，即痘苗病毒 K3 的 K45 和绵羊痘病毒 011 同源物的 Y47，对于病毒宿主种特异性至关重要。这些观察结果表明，痘病毒 K3 蛋白是病毒宿主特异性的主要决定因素。
