Division of Molecular and Cell Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Antiviral Res. 2013 Oct;100(1):259-68. doi: 10.1016/j.antiviral.2013.08.012. Epub 2013 Aug 28.
We have examined the role that hydroxymethylglutaryl coenzyme A reductase (HMGCR) plays during respiratory syncytial virus (RSV) maturation. Imaging analysis indicated that virus-induced changes in F-actin structure correlated with the formation of virus filaments, and that these virus filaments played a direct role in virus cell-to-cell transmission. Treatment with cytochalasin D (CYD) prevented virus filament formation and virus transmission, but this could be reversed by removal of CYD. This observation, together with the presence of F-actin within the virus filaments suggested that newly polymerised F-actin was required for virus transmission. The virus-induced change in F-actin was inhibited by the HMGCR inhibitor lovastatin, and this correlated with the inhibition of both virus filament formation and the incorporation of F-actin in these virus structures. Furthermore, this inhibitory effect on virus filament formation correlated with a significant reduction in RSV transmission. Collectively these data suggested that HMGCR-mediated changes in F-actin structure play an important role in the inter-cellular transmission of mature RSV particles. These data also highlighted the interplay between cellular metabolism and RSV transmission, and demonstrate that this interaction can be targeted using anti-virus strategies.
我们研究了羟甲基戊二酰辅酶 A 还原酶（HMGCR）在呼吸道合胞病毒（RSV）成熟过程中的作用。成像分析表明，病毒诱导的 F-肌动蛋白结构变化与病毒丝的形成相关，并且这些病毒丝在病毒细胞间传播中起直接作用。用细胞松弛素 D（CYD）处理可阻止病毒丝的形成和病毒传播，但 CYD 的去除可逆转这种作用。这一观察结果，加上病毒丝内存在 F-肌动蛋白，表明新聚合的 F-肌动蛋白是病毒传播所必需的。HMGCR 抑制剂洛伐他汀抑制病毒诱导的 F-肌动蛋白变化，这与病毒丝形成的抑制以及 F-肌动蛋白在这些病毒结构中的掺入相关。此外，这种对病毒丝形成的抑制作用与 RSV 传播的显著减少相关。综上所述，这些数据表明 HMGCR 介导的 F-肌动蛋白结构变化在成熟 RSV 颗粒的细胞间传播中起着重要作用。这些数据还强调了细胞代谢与 RSV 传播之间的相互作用，并证明可以使用抗病毒策略来靶向这种相互作用。
