Department of Molecular Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA, USA.
Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA.
J Gen Virol. 2023 Nov;104(11). doi: 10.1099/jgv.0.001913.
Human astroviruses (HAstVs) are small, non-enveloped icosahedral RNA viruses that are a significant cause of diarrhoea in young children. Despite their worldwide prevalence, HAstV pathogenesis studies and vaccine development remain challenging due to the lack of an animal model for HAstV infection. The recent development of a murine astrovirus (MuAstV) infection model in mice provides the opportunity to test proof-of-concept vaccines based on MuAstV antigens. To help establish a system in which an astrovirus capsid spike-based vaccine could be tested , we designed and produced a recombinant MuAstV capsid spike protein based on predicted secondary structure homology to HAstV spike proteins. The recombinant MuAstV spike can be expressed with high efficiency in and retains antigenicity to polyclonal antibodies elicited by MuAstV infection. We determined the crystal structure of the MuAstV spike to 1.75 Å and assessed its structural conservation with HAstV capsid spike. Despite low sequence identity between the MuAstV and HAstV spikes and differences in their overall shapes, they share related structural folds. Additionally, we found that vaccination with MuAstV spike induced anti-MuAstV-spike antibodies, highlighting that the recombinant spike is immunogenic. These studies lay a foundation for future MuAstV challenge studies to test whether MuAstV spike can be the basis of an effective vaccine.
人类星状病毒（HAstV）是一种小型、无包膜的二十面体 RNA 病毒，是导致幼儿腹泻的重要原因。尽管它们在全球范围内广泛存在，但由于缺乏 HAstV 感染的动物模型，HAstV 发病机制研究和疫苗开发仍然具有挑战性。最近在小鼠中开发的鼠星状病毒（MuAstV）感染模型为基于 MuAstV 抗原的疫苗提供了概念验证的机会。为了帮助建立一个可以测试基于星状病毒衣壳刺突的疫苗的系统，我们基于对 HAstV 刺突蛋白的预测二级结构同源性设计并生产了一种重组 MuAstV 衣壳刺突蛋白。该重组 MuAstV 刺突蛋白可以在 中高效表达，并保留对 MuAstV 感染诱导的多克隆抗体的抗原性。我们确定了 MuAstV 刺突的晶体结构至 1.75 Å，并评估了其与 HAstV 衣壳刺突的结构保守性。尽管 MuAstV 和 HAstV 刺突之间的序列同一性较低，并且它们的整体形状存在差异，但它们具有相关的结构折叠。此外，我们发现 MuAstV 刺突疫苗接种可诱导抗 MuAstV 刺突抗体，这突出表明重组刺突具有免疫原性。这些研究为未来的 MuAstV 挑战研究奠定了基础，以测试 MuAstV 刺突是否可以成为有效疫苗的基础。
