Abstract:
African swine fever virus (ASFV) is a large, double-stranded DNA virus that causes a fatal, contagious disease specifically in pigs. However, prevention and control of ASFV outbreaks have been hampered by the lack of an effective vaccine or antiviral treatment for ASFV. Although ASFV has been reported to adapt to a variety of continuous cell lines, the phenotypic and genetic changes associated with ASFV adaptation to MA-104 cells remain poorly understood. Here, we adapted ASFV field isolates to efficiently propagate through serial viral passages in MA-104 cells. The adapted ASFV strain developed a pronounced cytopathic effect and robust infection in MA-104 cells. Interestingly, the adapted variant maintained its tropism in primary porcine kidney macrophages. Whole genome analysis of the adapted virus revealed unique gene deletions in the left and right variable regions of the viral genome compared to other previously reported cell culture-adapted ASFV strains. Notably, gene duplications at the 5\' and 3\' ends of the viral genome were in reverse complementary alignment with their paralogs. Single point mutations in protein-coding genes and intergenic regions were also observed in the viral genome. Collectively, our results shed light on the significance of these unique genetic changes during adaptation, which facilitate the growth of ASFV in MA-104 cells.
摘要:
非洲猪瘟病毒(ASFV)是一种大型、双链DNA病毒导致致命的,特别是猪的传染病。然而,由于缺乏有效的ASFV疫苗或抗病毒治疗,ASFV暴发的预防和控制受到阻碍。虽然已报道ASFV适应多种连续细胞系,与ASFV适应MA-104细胞相关的表型和遗传变化仍然知之甚少。这里,我们调整了ASFV场分离株,使其在MA-104细胞中通过连续病毒传代有效繁殖.适应的ASFV菌株在MA-104细胞中产生了明显的细胞病变效应和强大的感染。有趣的是,适应的变体在原代猪肾巨噬细胞中保持了其嗜性。与先前报道的其他细胞培养物适应的ASFV毒株相比,适应的病毒的全基因组分析揭示了病毒基因组的左可变区和右可变区中的独特基因缺失。值得注意的是,病毒基因组5'和3'末端的基因重复与它们的旁系同源物反向互补排列。在病毒基因组中还观察到蛋白质编码基因和基因间区域的单点突变。总的来说,我们的结果揭示了适应过程中这些独特的遗传变化的重要性,促进ASFV在MA-104细胞中的生长。