Riad Sherief, Xiang Yan, AlDaif Basheer, Mercer Andrew A, Fleming Stephen B
Virus Research Unit, Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Front Microbiol. 2020 Jul 28;11:1797. doi: 10.3389/fmicb.2020.01797. eCollection 2020.
Type 1 interferons induce the upregulation of hundreds of interferon-stimulated genes (ISGs) that combat viral replication. The orf virus (ORFV) induces acute pustular skin lesions in sheep and goats and can reinfect its host, however, little is known of its ability to resist IFN. Vaccinia virus (VACV) encodes a number of factors that modulate the IFN response including the host-range genes and . A recombinant VACV-Western Reserve (WR) strain in which the and genes have been deleted does not replicate in cells treated with IFN-β nor in HeLa cells in which the IFN response is constitutive and is inhibited at the level of intermediate gene expression. Furthermore C7L is conserved in almost all poxviruses. We provide evidence that shows that although ORFV is more sensitive to IFN-β compared with VACV, and lacks homologues of and , it nevertheless has the ability to rescue a VACV KIL- C7L- gfp+ mutant in which gfp is expressed from a late promoter. Co-infection of HeLa cells with the mutant and ORFV demonstrated that ORFV was able to overcome the block in translation of intermediate transcripts in the mutant virus, allowing it to progress to late gene expression and new viral particles. Our findings strongly suggest that ORFV encodes a factor(s) that, although different in structure to C7L or KIL, targets an anti-viral cellular mechanism that is a highly potent at killing poxviruses.
1型干扰素可诱导数百种干扰素刺激基因（ISG）上调，这些基因可对抗病毒复制。口疮病毒（ORFV）可在绵羊和山羊中引发急性脓疱性皮肤损伤，并且能够再次感染其宿主，然而，人们对其抵抗干扰素的能力知之甚少。痘苗病毒（VACV）编码多种调节干扰素反应的因子，包括宿主范围基因和。一种缺失了和基因的重组痘苗病毒-西储（WR）株，在经干扰素-β处理的细胞中以及在干扰素反应呈组成性且在中间基因表达水平受到抑制的HeLa细胞中均无法复制。此外，C7L在几乎所有痘病毒中都是保守的。我们提供的证据表明，尽管与痘苗病毒相比，口疮病毒对干扰素-β更为敏感，并且缺乏和的同源物，但它仍然有能力拯救一种痘苗病毒KIL-C7L-gfp+突变体，其中绿色荧光蛋白（gfp）由晚期启动子表达。突变体与口疮病毒共同感染HeLa细胞表明，口疮病毒能够克服突变病毒中间转录本翻译的障碍，使其能够进入晚期基因表达并产生新的病毒颗粒。我们的研究结果强烈表明，口疮病毒编码一种因子，尽管其结构与C7L或KIL不同，但靶向一种抗病毒细胞机制，该机制在杀死痘病毒方面非常有效。
