National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Beijing Productivity Center, Major Project Department, Beijing, 100088, China.
Nat Commun. 2018 Nov 26;9(1):4985. doi: 10.1038/s41467-018-07531-0.
Coxsackievirus A10 (CVA10), a human type-A Enterovirus (HEV-A), can cause diseases ranging from hand-foot-and-mouth disease to polio-myelitis-like disease. CVA10, together with some other HEV-As, utilizing the molecule KREMEN1 as an entry receptor, constitutes a KREMEN1-dependent subgroup within HEV-As. Currently, there is no vaccine or antiviral therapy available for treating diseases caused by CVA10. The atomic-resolution structure of the CVA10 virion, which is within the KREMEN1-dependent subgroup, shows significant conformational differences in the putative receptor binding sites and serotype-specific epitopes, when compared to the SCARB2-dependent subgroup of HEV-A, such as EV71, highlighting specific differences between the sub-groups. We also report two expanded structures of CVA10, an empty particle and uncoating intermediate at atomic resolution, as well as a medium-resolution genome structure reconstructed using a symmetry-mismatch method. Structural comparisons coupled with previous results, reveal an ordered signal transmission process for enterovirus uncoating, converting exo-genetic receptor-attachment inputs into a generic RNA release mechanism.
柯萨奇病毒 A10（CVA10）是一种人类肠道病毒 A 型（HEV-A），可引起手足口病到脊髓灰质炎样疾病等多种疾病。CVA10 与其他一些 HEV-A 型病毒一起，利用分子 KREMEN1 作为进入受体，构成了 HEV-A 中的 KREMEN1 依赖亚群。目前，尚无针对 CVA10 引起的疾病的疫苗或抗病毒疗法。CVA10 病毒粒子的原子分辨率结构，属于 KREMEN1 依赖亚群，与 SCARB2 依赖亚群（如 EV71）的 HEV-A 相比，在假定的受体结合位点和血清型特异性表位方面显示出显著的构象差异，突出了亚群之间的特定差异。我们还报告了 CVA10 的两个扩展结构，即原子分辨率下的空粒子和脱壳中间态，以及使用对称失配方法重建的中分辨率基因组结构。结构比较结合以前的结果，揭示了肠道病毒脱壳的有序信号转导过程，将外遗传受体附着的输入转化为通用的 RNA 释放机制。
