Packaging signals (pac1 and pac2) of human herpesviruses (HHVs) that contain GC-rich elements are essential for cleavage and packaging of the virus. Here, we report the presence of putative G-quadruplex sequences (PQSs) in the packaging signal (pac1) of all HHVs. Importantly, the residues critical for the formation of G-quadruplex structures were highly conserved as compared to those not critical for the formation of this DNA secondary structure, indicating that G-quadruplexes are positively selected within pac1 in the evolution of herpesviruses. CD spectroscopy, NMR spectroscopy, native/denaturing gel, and DMS footprinting confirmed the formation of G-quadruplex structures in all pac1 PQS oligonucleotides analyzed; the majority of the PQS had the propensity to form intermolecular structures. The presence of highly conserved G-quadruplex motifs at genomic locations critical for virus packaging has not been previously recognized. Our findings provide a new perspective on the putative functions of G-quadruplexes in virus genomes.

中文翻译：

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人类疱疹病毒的Pac1信号包含高度保守的G四联体基序。

包含富含GC元素的人疱疹病毒（HHV）的包装信号（pac1和pac2）对于病毒的切割和包装至关重要。在这里，我们报告所有HHV的包装信号（pac1）中存在假定的G四联体序列（PQS）。重要的是，与对于形成该DNA二级结构不是至关重要的那些残基相比，对于形成G-四链体至关重要的残基是高度保守的，这表明在疱疹病毒的进化中，在pac1内肯定地选择了G-四链体。CD光谱，NMR光谱，天然/变性凝胶和DMS足迹证实了在所有pac1中均形成了G-四链体结构分析了PQS寡核苷酸; 大多数PQS倾向于形成分子间结构。以前尚未认识到在病毒包装至关重要的基因组位置存在高度保守的G-四链体基序。我们的发现为病毒基因组中G-四链体的假定功能提供了新的视角。