CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
J Virol. 2024 Mar 19;98(3):e0153623. doi: 10.1128/jvi.01536-23. Epub 2024 Feb 5.
African swine fever (ASF) is a highly contagious viral disease that affects domestic and wild pigs. The causative agent of ASF is African swine fever virus (ASFV), a large double-stranded DNA virus with a complex virion structure. Among the various proteins encoded by ASFV, A137R is a crucial structural protein associated with its virulence. However, the structure and molecular mechanisms underlying the functions of A137R remain largely unknown. In this study, we present the structure of A137R determined by cryogenic electron microscopy single-particle reconstruction, which reveals that A137R self-oligomerizes to form a dodecahedron-shaped cage composed of 60 polymers. The dodecahedron is literally equivalent to a 1 icosahedron where the icosahedral vertexes are located in the center of each dodecahedral facet. Within each facet, five A137R protomers are arranged in a head-to-tail orientation with a long N-terminal helix forming the edge through which adjacent facets stitch together to form the dodecahedral cage. Combining structural analysis and biochemical evidence, we demonstrate that the N-terminal domain of A137R is crucial and sufficient for mediating the assembly of the dodecahedron. These findings imply the role of A137R cage as a core component in the icosahedral ASFV virion and suggest a promising molecular scaffold for nanotechnology applications.
African swine fever (ASF) is a lethal viral disease of pigs caused by African swine fever virus (ASFV). No commercial vaccines and antiviral treatments are available for the prevention and control of the disease. A137R is a structural protein of ASFV that is associated with its virulence. The discovery of the dodecahedron-shaped cage structure of A137R in this study is of great importance in understanding ASFV pathogenicity. This finding sheds light on the molecular mechanisms underlying the functions of A137R. Furthermore, the dodecahedral cage formed by A137R shows promise as a molecular scaffold for nanoparticle vectors. Overall, this study provides valuable insights into the structure and function of A137R, contributing to our understanding of ASFV and potentially opening up new avenues for the development of vaccines or treatments for ASF.
非洲猪瘟（ASF）是一种高度传染性的病毒性疾病，影响家猪和野猪。ASF 的病原体是非洲猪瘟病毒（ASFV），这是一种具有复杂病毒粒子结构的大型双链 DNA 病毒。在 ASFV 编码的各种蛋白质中，A137R 是与毒力相关的关键结构蛋白。然而，A137R 的结构和分子机制及其功能仍然知之甚少。在这项研究中，我们通过低温电子显微镜单颗粒重建技术确定了 A137R 的结构，该结构显示 A137R 自组装形成由 60 个聚合物组成的十二面体笼。这个十二面体实际上相当于一个二十面体，其中二十面体的顶点位于每个十二面体面的中心。在每个面内，五个 A137R 原聚体以头到尾的方式排列，长的 N 端螺旋形成边缘，相邻的面通过这个边缘缝合在一起形成十二面体笼。结合结构分析和生化证据，我们证明 A137R 的 N 端结构域对于介导十二面体的组装至关重要且充分。这些发现表明 A137R 笼作为二十面体 ASFV 病毒粒子的核心成分的作用，并为纳米技术应用提供了有前途的分子支架。
非洲猪瘟（ASF）是由非洲猪瘟病毒（ASFV）引起的一种致命猪病。目前尚无用于预防和控制该疾病的商业疫苗和抗病毒治疗方法。A137R 是 ASFV 的一种结构蛋白，与病毒的毒力有关。本研究发现 A137R 的十二面体笼状结构具有重要意义，有助于了解 ASFV 的致病性。这一发现揭示了 A137R 功能的分子机制。此外，A137R 形成的十二面体笼有望成为纳米颗粒载体的分子支架。总的来说，这项研究为 A137R 的结构和功能提供了有价值的见解，有助于我们理解 ASFV，并为 ASF 的疫苗或治疗方法的开发开辟新的途径。
