Kozlovskaya Liubov I, Osolodkin Dmitry I, Tuchynskaya Ksenia K, Shevtsova Anastasia S, Okhezin Egor V, Palyulin Vladimir A, Nikitin Nikolai A, Karganova Galina G
FSASI "Chumakov FSC R&D IBP RAS" (Institute of Poliomyelitis), Moscow, 108819, Russia.
Institute of Translational Medicine and Biotechnology, Sechenov First Moscow State Medical University, Trubetskaya 8, Moscow, 119991, Russia.
Arch Virol. 2023 Mar 5;168(3):100. doi: 10.1007/s00705-023-05728-3.
Introduction of point mutations is one of the forces enabling arboviruses to rapidly adapt in a changing environment. The influence of these mutations on the properties of the virus is not always obvious. In this study, we attempted to clarify this influence using an in silico approach. Using molecular dynamics (MD) simulations, we investigated how the position of charge-changing point mutations influences the structure and conformational stability of the E protein for a set of variants of a single TBEV strain. The computational findings were supported by experimental evaluation of relevant properties of virions, such as binding to heparan sulfate, thermostability, and susceptibility of the viral hemagglutinating activity to detergents. Our results also point to relationships between E protein dynamics and viral neuroinvasiveness.
引入点突变是使虫媒病毒能够在不断变化的环境中快速适应的因素之一。这些突变对病毒特性的影响并不总是显而易见的。在本研究中,我们试图使用计算机模拟方法来阐明这种影响。通过分子动力学(MD)模拟,我们研究了电荷改变点突变的位置如何影响单个蜱传脑炎病毒(TBEV)毒株一组变体的E蛋白的结构和构象稳定性。计算结果得到了病毒粒子相关特性的实验评估的支持,如与硫酸乙酰肝素的结合、热稳定性以及病毒血凝活性对去污剂的敏感性。我们的结果还指出了E蛋白动力学与病毒神经侵袭性之间的关系。