Abstract：
Human cytomegalovirus (HCMV) replication relies on a nucleocapsid coat of the 150 kDa, subfamily-specific tegument phosphoprotein (pp150) to regulate cytoplasmic virion maturation. While recent structural studies revealed pp150-capsid interactions, the role of specific amino-acids involved in these interactions have not been established experimentally. In this study, pp150 and the small capsid protein (SCP), one of pp150\'s binding partners found atop the major capsid protein (MCP), were subjected to mutational and structural analyses. Mutations to clusters of polar or hydrophobic residues along the pp150-SCP interface abolished viral replication, with no replication detected in mutant virus-infected cells. Notably, a single amino acid mutation (pp150 K255E) at the pp150-MCP interface significantly attenuated viral replication, unlike in pp150-deletion mutants where capsids degraded outside host nuclei. These functionally significant mutations targeting pp150-capsid interactions, particularly the pp150 K255E replication-attenuated mutant, can be explored to overcome the historical challenges of developing effective antivirals and vaccines against HCMV infection.
摘要：
人巨细胞病毒（HCMV）的复制依赖于150kDa的核衣壳，亚家族特异性膜磷蛋白（pp150）调节细胞质病毒体成熟。虽然最近的结构研究揭示了pp150-衣壳相互作用，参与这些相互作用的特定氨基酸的作用尚未通过实验确定。在这项研究中,pp150和小衣壳蛋白（SCP），在主要衣壳蛋白（MCP）上发现的pp150结合伴侣之一，进行了突变和结构分析。沿着pp150-SCP界面的极性或疏水残基簇的突变消除了病毒复制，在突变病毒感染的细胞中没有检测到复制。值得注意的是,在pp150-MCP界面的单个氨基酸突变（pp150K255E）显着减弱病毒复制，与pp150缺失突变体不同，衣壳在宿主核外降解。这些功能上显著的突变靶向pp150-衣壳相互作用，特别是pp150K255E复制减毒突变体，可以探索克服开发针对HCMV感染的有效抗病毒药物和疫苗的历史挑战。
