Krafčíková Petra, Demkovičová Erika, Halaganová Andrea, Víglaský Viktor
Department of Biochemistry, Institute of Chemistry, Faculty of Sciences, P. J. Safarik University, 04001 Kosice, Slovakia.
J Nucleic Acids. 2017;2017:6513720. doi: 10.1155/2017/6513720. Epub 2017 Dec 31.
The HIV virus is one of the most studied viruses in the world. This is especially true in terms of gene sequencing, and to date more than 9 thousand genomic sequences of HIV isolates have been sequenced and analyzed. In this study, a series of DNA sequences, which have the potential to form G-quadruplex structures, is analyzed. Several such sequences were found in various coding and noncoding virus domains, including the U3 LTR, tat, rev, env, and vpx regions. Interestingly, a homological sequence to the already well-known HIV integrase aptamer was identified in the minus-strand. The sequences derived from original isolates were analyzed using standard spectral and electrophoretic methods. In addition, a recently developed methodology is applied which uses induced circular dichroism spectral profiles of G-quadruplex-ligand (Thiazole Orange) complexes to determine if G-rich sequences can adopt G-quadruplex structure. Targeting the G-quadruplexes or peptide domains corresponding to the G-rich coding sequence in HIV offers researchers attractive therapeutic targets which would be of particular use in the development of novel antiviral therapies. The analysis of G-rich regions can provide researchers with a path to find specific targets which could be of interest for specific types of virus.
人类免疫缺陷病毒（HIV）是世界上研究最多的病毒之一。在基因测序方面尤其如此，迄今为止，已对9000多个HIV分离株的基因组序列进行了测序和分析。在本研究中，对一系列有可能形成G-四链体结构的DNA序列进行了分析。在各种编码和非编码病毒结构域中发现了几个这样的序列，包括U3长末端重复序列（LTR）、反式激活因子（tat）、病毒蛋白表达调节因子（rev）、包膜蛋白（env）和病毒感染因子（vpx）区域。有趣的是，在负链中鉴定出了与已熟知的HIV整合酶适体的同源序列。使用标准光谱和电泳方法分析了来自原始分离株的序列。此外，还应用了一种最近开发的方法，该方法利用G-四链体-配体（噻唑橙）复合物的诱导圆二色光谱谱来确定富含G的序列是否可以形成G-四链体结构。针对HIV中与富含G的编码序列相对应的G-四链体或肽结构域为研究人员提供了有吸引力的治疗靶点，这在新型抗病毒疗法的开发中将特别有用。对富含G的区域进行分析可以为研究人员提供一条找到特定靶点的途径，这些靶点可能对特定类型的病毒有意义。
