Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, USA.
Rev Med Virol. 2018 May;28(3):e1972. doi: 10.1002/rmv.1972. Epub 2018 Mar 24.
Herpesviruses (Herpesvirales) and tailed bacteriophages (Caudovirales) package their dsDNA genomes through an evolutionarily conserved mechanism. Much is known about the biochemistry and structural biology of phage portal proteins and the DNA encapsidation (viral genome cleavage and packaging) process. Although not at the same level of detail, studies on HSV-1, CMV, VZV, and HHV-8 have revealed important information on the function and structure of herpesvirus portal proteins. During dsDNA phage and herpesviral genome replication, concatamers of viral dsDNA are cleaved into single length units by a virus-encoded terminase and packaged into preformed procapsids through a channel located at a single capsid vertex (portal). Oligomeric portals are formed by the interaction of identical portal protein monomers. Comparing portal protein primary aa sequences between phage and herpesviruses reveals little to no sequence similarity. In contrast, the secondary and tertiary structures of known portals are remarkable. In all cases, function is highly conserved in that portals are essential for DNA packaging and also play a role in releasing viral genomic DNA during infection. Preclinical studies have described small molecules that target the HSV-1 and VZV portals and prevent viral replication by inhibiting encapsidation. This review summarizes what is known concerning the structure and function of herpesvirus portal proteins primarily based on their conserved bacteriophage counterparts and the potential to develop novel portal-specific DNA encapsidation inhibitors.
疱疹病毒（疱疹病毒目）和有尾噬菌体（长尾噬菌体目）通过一种进化上保守的机制包装其双链 DNA 基因组。噬菌体门户蛋白的生物化学和结构生物学以及 DNA 封装（病毒基因组切割和包装）过程的研究已经有很多了解。尽管没有达到相同的详细程度，但对 HSV-1、CMV、VZV 和 HHV-8 的研究揭示了疱疹病毒门户蛋白功能和结构的重要信息。在双链 DNA 噬菌体和疱疹病毒基因组复制过程中，病毒编码的末端酶将病毒双链 DNA 的串联体切割成单个长度单位，并通过位于单个衣壳顶点（门户）的通道包装到预先形成的原衣壳中。多聚体门户通过相同门户蛋白单体的相互作用形成。比较噬菌体和疱疹病毒之间的门户蛋白初级氨基酸序列，发现几乎没有序列相似性。相比之下，已知门户的二级和三级结构非常显著。在所有情况下，功能都高度保守，即门户对于 DNA 包装是必不可少的，并且在感染过程中释放病毒基因组 DNA 也发挥作用。临床前研究已经描述了靶向 HSV-1 和 VZV 门户的小分子，并通过抑制封装来阻止病毒复制。本综述主要基于其保守的噬菌体对应物总结了关于疱疹病毒门户蛋白的结构和功能的已知信息，以及开发新型门户特异性 DNA 封装抑制剂的潜力。
