Goh Gerard Kian-Meng, Dunker A Keith, Uversky Vladimir N
Goh's BioComputing, Singapore, Republic of Singapore.
Indiana University School of Medicine, Indianapolis, Indiana, USA.
Mol Biosyst. 2016 May 24;12(6):1881-91. doi: 10.1039/c6mb00228e.
Computational analyses revealed correlations between the intrinsic disorder propensity of shell proteins and case fatality rates (CFRs) among Flaviviruses and within at least two Flavivirus species, such as tick-borne encephalitis virus (TBEV) and dengue virus (DENV). The shell proteins analyzed in this study are capsid (C) and membrane (PrM, Pr, and M) proteins. The highest correlations can be found when regression analyses were conducted using Pr (Flavivirus: r(2) = 0.78, p < 0.01) or M (Flavivirus: r(2) = 0.91, p < 0.01) as an independent variable with C and CFR as co-explanatory and dependent variables, respectively. Interestingly, while predicted intrinsic disorder levels (PIDs) of both C and M are positively correlated with the virulence, the PIDs of Pr and CFR are negatively correlated. This is likely due to the fact that the Pr portion of PrM plays various roles in protecting the virion from damage, whereas M and C are assisted by greater potential in binding promiscuity as a result of greater disorder. The C protein of yellow fever virus (YFV), which is the most virulent virus in the sample, has the highest PID levels, whereas the second most virulent TBEV FE subtype has the second highest PID score due to its C protein, and the least virulent West Nile virus (WNV) has the least disordered C protein. This knowledge can be used while working on the development and identification of attenuated strains for vaccine. Curiously, unlike Flaviviruses, a disordered outer shell was described for hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human simplex virus 2 (HSV-2), which currently have no effective vaccine.
计算分析揭示了黄病毒属病毒以及至少两种黄病毒（如蜱传脑炎病毒（TBEV）和登革热病毒（DENV））中壳蛋白的内在无序倾向与病死率（CFR）之间的相关性。本研究中分析的壳蛋白是衣壳（C）蛋白和膜（PrM、Pr和M）蛋白。当以Pr（黄病毒属：r(2)=0.78，p<0.01）或M（黄病毒属：r(2)=0.91，p<0.01）作为自变量，C和CFR分别作为共同解释变量和因变量进行回归分析时，可发现最高的相关性。有趣的是，虽然C和M的预测内在无序水平（PID）均与毒力呈正相关，但Pr和CFR的PID呈负相关。这可能是由于PrM的Pr部分在保护病毒粒子免受损伤方面发挥着多种作用，而M和C由于更高的无序性在结合多配性方面具有更大的潜力。样本中毒力最强的黄热病毒（YFV）的C蛋白具有最高的PID水平，而毒力第二强的TBEV FE亚型由于其C蛋白具有第二高的PID分数，毒力最弱的西尼罗河病毒（WNV）的C蛋白无序性最低。这些知识可用于疫苗减毒株的开发和鉴定。奇怪的是，与黄病毒属不同，丙型肝炎病毒（HCV）、人类免疫缺陷病毒（HIV）和单纯疱疹病毒2型（HSV-2）被描述为具有无序外壳，目前尚无有效的疫苗。
