California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Nat Commun. 2021 Sep 17;12(1):5513. doi: 10.1038/s41467-021-25791-1.
Under the Baltimore nucleic acid-based virus classification scheme, the herpesvirus human cytomegalovirus (HCMV) is a Class I virus, meaning that it contains a double-stranded DNA genome-and no RNA. Here, we report sub-particle cryoEM reconstructions of HCMV virions at 2.9 Å resolution revealing structures resembling non-coding transfer RNAs (tRNAs) associated with the virion's capsid-bound tegument protein, pp150. Through deep sequencing, we show that these RNA sequences match human tRNAs, and we built atomic models using the most abundant tRNA species. Based on our models, tRNA recruitment is mediated by the electrostatic interactions between tRNA phosphate groups and the helix-loop-helix motif of HCMV pp150. The specificity of these interactions may explain the absence of such tRNA densities in murine cytomegalovirus and other human herpesviruses.
根据巴尔的摩核酸分类方案,人类巨细胞病毒(HCMV)是一种 I 类病毒,这意味着它含有双链 DNA 基因组,而没有 RNA。在这里,我们报告了 HCMV 病毒粒子的亚颗粒冷冻电镜重建,分辨率为 2.9 Å,揭示了与病毒衣壳结合的被膜蛋白 pp150 相关的类似非编码转移 RNA(tRNA)的结构。通过深度测序,我们表明这些 RNA 序列与人类 tRNA 相匹配,并且我们使用最丰富的 tRNA 物种构建了原子模型。基于我们的模型,tRNA 的募集是由 tRNA 磷酸盐基团与 HCMV pp150 的螺旋-环-螺旋结构之间的静电相互作用介导的。这些相互作用的特异性可能解释了在鼠巨细胞病毒和其他人类疱疹病毒中不存在这种 tRNA 密度的原因。