Caddy Sarah, Papa Guido, Borodavka Alexander, Desselberger Ulrich
Cambridge Institute for Therapeutic Immunology and Infectious Disease Jeffery Cheah Biomedical Centre, Cambridge, CB2 0AW, UK.
MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Virus Res. 2021 Oct 15;304:198499. doi: 10.1016/j.virusres.2021.198499. Epub 2021 Jul 2.
Rotaviruses are major causes of acute gastroenteritis in infants and young children worldwide and also cause disease in the young of many other mammalian and of avian species. During the recent 5-6 years rotavirus research has benefitted in a major way from the establishment of plasmid only-based reverse genetics systems, the creation of human and other mammalian intestinal enteroids, and from the wide application of structural biology (cryo-electron microscopy, cryo-EM tomography) and complementary biophysical approaches. All of these have permitted to gain new insights into structure-function relationships of rotaviruses and their interactions with the host. This review follows different stages of the viral replication cycle and summarizes highlights of structure-function studies of rotavirus-encoded proteins (both structural and non-structural), molecular mechanisms of viral replication including involvement of cellular proteins and lipids, the spectrum of viral genomic and antigenic diversity, progress in understanding of innate and acquired immune responses, and further developments of prevention of rotavirus-associated disease.
轮状病毒是全球婴幼儿急性胃肠炎的主要病因,也可导致许多其他哺乳动物和鸟类幼崽发病。在最近5至6年里,轮状病毒研究在很大程度上受益于仅基于质粒的反向遗传学系统的建立、人类和其他哺乳动物肠道类器官的创建,以及结构生物学(冷冻电子显微镜、冷冻电镜断层扫描)和互补生物物理方法的广泛应用。所有这些都使人们对轮状病毒的结构-功能关系及其与宿主的相互作用有了新的认识。本综述遵循病毒复制周期的不同阶段,总结了轮状病毒编码蛋白(结构蛋白和非结构蛋白)的结构-功能研究亮点、病毒复制的分子机制,包括细胞蛋白和脂质的参与情况、病毒基因组和抗原多样性的范围、在理解先天免疫和获得性免疫反应方面的进展,以及预防轮状病毒相关疾病的进一步发展。