Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65, Brno, Czech Republic.
Faculty of Chemistry, Brno University of Technology, Purkyňova 118, 612 00, Brno, Czech Republic.
BMC Genomics. 2021 Jan 23;22(1):77. doi: 10.1186/s12864-021-07377-9.
Influenza viruses are dangerous pathogens. Seventy-Seven genomes of recently emerged genotype 4 reassortant Eurasian avian-like H1N1 virus (G4-EA-H1N1) are currently available. We investigated the presence and variation of potential G-quadruplex forming sequences (PQS), which can serve as targets for antiviral treatment.
PQS were identified in all 77 genomes. The total number of PQS in G4-EA-H1N1 genomes was 571. Interestingly, the number of PQS per genome in individual close relative viruses varied from 4 to 12. PQS were not randomly distributed in the 8 segments of the G4-EA-H1N1 genome, the highest frequency of PQS being found in the NP segment (1.39 per 1000 nt), which is considered a potential target for antiviral therapy. In contrast, no PQS was found in the NS segment. Analyses of variability pointed the importance of some PQS; even if genome variation of influenza virus is extreme, the PQS with the highest G4Hunter score is the most conserved in all tested genomes. G-quadruplex formation in vitro was experimentally confirmed using spectroscopic methods.
The results presented here hint several G-quadruplex-forming sequences in G4-EA-H1N1 genomes, that could provide good therapeutic targets.
流感病毒是危险的病原体。目前有 77 个最近出现的基因型 4 重组欧亚禽源 H1N1 病毒(G4-EA-H1N1)的基因组。我们研究了潜在的 G-四链体形成序列(PQS)的存在和变异,这些序列可以作为抗病毒治疗的靶点。
在所有 77 个基因组中都鉴定出了 PQS。G4-EA-H1N1 基因组中的 PQS 总数为 571 个。有趣的是,单个近亲病毒中每个基因组的 PQS 数量从 4 到 12 不等。PQS 在 G4-EA-H1N1 基因组的 8 个片段中并非随机分布,NP 片段中的 PQS 频率最高(每 1000nt 有 1.39 个),这被认为是抗病毒治疗的潜在靶点。相比之下,NS 片段中没有 PQS。变异分析指出了一些 PQS 的重要性;即使流感病毒的基因组变异极为极端,但在所有测试的基因组中,G4Hunter 得分最高的 PQS 是最保守的。使用光谱方法实验证实了体外 G-四链体的形成。
这里呈现的结果提示 G4-EA-H1N1 基因组中有几个形成 G-四链体的序列,这些序列可能提供很好的治疗靶点。