Criglar Jeanette M, Estes Mary K, Crawford Sue E
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States.
Department of Medicine, Baylor College of Medicine, Houston, TX, United States.
Front Physiol. 2022 Mar 23;13:836870. doi: 10.3389/fphys.2022.836870. eCollection 2022.
A variety of pathogens, including viruses, bacteria and parasites, target cellular lipid droplets for their replication. Rotaviruses (RVs) infect the villous epithelium of the small intestine and are a major cause of acute gastroenteritis in infants and young children worldwide. RVs induce and require lipid droplets for the formation of viroplasms, sites of virus genome replication, and nascent particle assembly. Here we review the role of lipid droplets in RV replication. Inhibitors of fatty acid synthesis or chemicals that interfere with lipid droplet homeostasis decrease the number and size of viroplasms and the yield of infectious virus. We used a genetically engineered RV, delayed in viroplasm assembly, to show an early interaction of RV nonstructural protein NSP2 and the lipid droplet-associated protein phospho-PLIN1. The interaction between NSP2 and phospho-PLIN1 suggests that we have identified part of the mechanism of RV-induced lipid droplet formation. These studies demonstrate that RV is an excellent model to dissect the cellular process of lipid droplet formation and to determine how RV induces and usurps lipid droplet biogenesis to form viroplasm/lipid droplets for virus replication.
包括病毒、细菌和寄生虫在内的多种病原体，会将细胞脂滴作为其复制的靶点。轮状病毒（RVs）感染小肠绒毛上皮，是全球婴幼儿急性胃肠炎的主要病因。RVs诱导并需要脂滴来形成病毒工厂，即病毒基因组复制和新生病毒颗粒组装的场所。在此，我们综述脂滴在RV复制中的作用。脂肪酸合成抑制剂或干扰脂滴稳态的化学物质会减少病毒工厂的数量和大小以及感染性病毒的产量。我们使用了一种在病毒工厂组装方面延迟的基因工程RV，以显示RV非结构蛋白NSP2与脂滴相关蛋白磷酸化的PLIN1之间的早期相互作用。NSP2与磷酸化的PLIN1之间的相互作用表明，我们已经确定了RV诱导脂滴形成机制的一部分。这些研究表明，RV是剖析脂滴形成的细胞过程以及确定RV如何诱导和利用脂滴生物发生以形成用于病毒复制的病毒工厂/脂滴的极佳模型。
