Department of Biochemistry, University of Wisconsin, Madison, WI, USA.
Cryo-Electron Microscopy Research Center, Department of Biochemistry, University of Wisconsin, Madison, WI, USA.
Nat Commun. 2024 Jul 14;15(1):5923. doi: 10.1038/s41467-024-50162-x.
Respiratory syncytial virus (RSV) is an enveloped, filamentous, negative-strand RNA virus that causes significant respiratory illness worldwide. RSV vaccines are available, however there is still significant need for research to support the development of vaccines and therapeutics against RSV and related Mononegavirales viruses. Individual virions vary in size, with an average diameter of ~130 nm and ranging from ~500 nm to over 10 µm in length. Though the general arrangement of structural proteins in virions is known, we use cryo-electron tomography and sub-tomogram averaging to determine the molecular organization of RSV structural proteins. We show that the peripheral membrane-associated RSV matrix (M) protein is arranged in a packed helical-like lattice of M-dimers. We report that RSV F glycoprotein is frequently observed as pairs of trimers oriented in an anti-parallel conformation to support potential interactions between trimers. Our sub-tomogram averages indicate the positioning of F-trimer pairs is correlated with the underlying M lattice. These results provide insight into RSV virion organization and may aid in the development of RSV vaccines and anti-viral targets.
呼吸道合胞病毒（RSV）是一种包膜、丝状、负链 RNA 病毒，可导致全球范围内严重的呼吸道疾病。目前已有 RSV 疫苗，但仍需要大量研究来支持 RSV 和相关 Mononegavirales 病毒疫苗和疗法的开发。单个病毒粒子的大小不同，平均直径约为 130nm，长度从 500nm 到 10μm 以上不等。尽管已知病毒粒子中结构蛋白的一般排列方式，但我们使用冷冻电镜断层扫描和子断层平均法来确定 RSV 结构蛋白的分子组织。我们表明，外周膜相关的 RSV 基质（M）蛋白以 M-二聚体的堆积螺旋状晶格排列。我们报告说，RSV F 糖蛋白经常观察到成对的三聚体以反平行构象取向，以支持三聚体之间的潜在相互作用。我们的子断层平均表明，F-三聚体对的定位与底层 M 晶格相关。这些结果提供了对 RSV 病毒粒子组织的深入了解，并可能有助于 RSV 疫苗和抗病毒靶点的开发。
