Bohálová Natália, Cantara Alessio, Bartas Martin, Kaura Patrik, Šťastný Jiří, Pečinka Petr, Fojta Miroslav, Mergny Jean-Louis, Brázda Václav
Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, Brno, 612 65, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, 62500, Brno, Czech Republic.
Department of Biology and Ecology/Institute of Environmental Technologies, Faculty of Science, University of Ostrava, Ostrava, 710 00, Czech Republic.
Biochimie. 2021 Jul;186:13-27. doi: 10.1016/j.biochi.2021.03.017. Epub 2021 Apr 9.
G-quadruplexes contribute to the regulation of key molecular processes. Their utilization for antiviral therapy is an emerging field of contemporary research. Here we present comprehensive analyses of the presence and localization of putative G-quadruplex forming sequences (PQS) in all viral genomes currently available in the NCBI database (including subviral agents). The G4Hunter algorithm was applied to a pool of 11,000 accessible viral genomes representing 350 Mbp in total. PQS frequencies differ across evolutionary groups of viruses, and are enriched in repeats, replication origins, 5'UTRs and 3'UTRs. Importantly, PQS presence and localization is connected to viral lifecycles and corresponds to the type of viral infection rather than to nucleic acid type; while viruses routinely causing persistent infections in Metazoa hosts are enriched for PQS, viruses causing acute infections are significantly depleted for PQS. The unique localization of PQS identifies the importance of G-quadruplex-based regulation of viral replication and life cycle, providing a tool for potential therapeutic targeting.
G-四链体有助于关键分子过程的调控。将其用于抗病毒治疗是当代研究中一个新兴的领域。在此，我们对NCBI数据库中目前可获取的所有病毒基因组（包括亚病毒因子）中假定的G-四链体形成序列（PQS）的存在情况和定位进行了全面分析。G4Hunter算法被应用于一组总计代表350兆碱基对的11,000个可获取的病毒基因组。PQS频率在病毒的进化群体中有所不同，并且在重复序列、复制起点、5'非翻译区和3'非翻译区中富集。重要的是，PQS的存在和定位与病毒生命周期相关，并且与病毒感染类型相对应，而非与核酸类型相对应；在后生动物宿主中经常引起持续性感染的病毒富含PQS，而引起急性感染的病毒则显著缺乏PQS。PQS的独特定位确定了基于G-四链体的病毒复制和生命周期调控的重要性，为潜在的治疗靶点提供了一种工具。
