Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Center for Food Animal Health, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH 44691, USA.
Viruses. 2023 Oct 17;15(10):2107. doi: 10.3390/v15102107.
Influenza A virus (IAV) populations harbor large subpopulations of defective-interfering particles characterized by internally deleted viral genomes. These internally deleted genomes have demonstrated the ability to suppress infectivity and boost innate immunity, rendering them promising for therapeutic and immunogenic applications. In this study, we aimed to investigate the diversity and complexity of the internally deleted IAV genomes within a panel of plaque-purified avian influenza viruses selected for their enhanced interferon-inducing phenotypes. Our findings unveiled that the abundance and diversity of internally deleted viral genomes were contingent upon the viral subculture and plaque purification processes. We observed a heightened occurrence of internally deleted genomes with distinct junctions in viral clones exhibiting enhanced interferon-inducing phenotypes, accompanied by additional truncation in the nonstructural 1 protein linker region (NS1Δ76-86). Computational analyses suggest the internally deleted IAV genomes can encode a broad range of carboxy-terminally truncated and intrinsically disordered proteins with variable lengths and amino acid composition. Further research is imperative to unravel the underlying mechanisms driving the increased diversity of internal deletions within the genomes of viral clones exhibiting enhanced interferon-inducing capacities and to explore their potential for modulating cellular processes and immunity.
甲型流感病毒（IAV）群体中存在大量特征为内部缺失病毒基因组的缺陷干扰粒子亚群。这些内部缺失的基因组已被证明具有抑制感染性和增强先天免疫的能力，因此具有治疗和免疫原性应用的潜力。在这项研究中，我们旨在研究一组为增强干扰素诱导表型而选择的斑块纯化禽流感病毒中内部缺失的 IAV 基因组的多样性和复杂性。我们的研究结果表明，内部缺失的病毒基因组的丰度和多样性取决于病毒的亚培养和斑块纯化过程。我们观察到具有增强干扰素诱导表型的病毒克隆中内部缺失基因组的出现频率更高，并且具有独特的连接点，同时非结构蛋白 1 蛋白连接区（NS1Δ76-86）也发生了额外的截断。计算分析表明，内部缺失的 IAV 基因组可以编码广泛的羧基末端截断和固有无序的蛋白质，其长度和氨基酸组成可变。进一步的研究对于揭示具有增强干扰素诱导能力的病毒克隆基因组中内部缺失增加的多样性的潜在机制以及探索它们调节细胞过程和免疫的潜力至关重要。
