背景:黄病毒在人类中引起严重的脑炎或出血性疾病。其成员,Kyasanur森林病病毒(KFDV)和Alkhumra出血热病毒(ALKV),引起出血热,在印度和沙特阿拉伯很普遍,分别,而蜱传脑炎病毒(TBEV)在欧洲和亚洲引起危险的脑炎感染。然而,关于这些致命病毒的免疫反应目标的信息很少。这里,我们预测了病毒包膜蛋白的潜在抗原肽表位,用于诱导细胞介导和体液免疫应答。
方法:使用免疫表位数据库和分析资源(IEDB-AR),我们在KFDV和ALKV中鉴定出13个MHC-I和2个MHC-II优势保守表位,在TBEV包膜蛋白中鉴定出6个MHC-I和3个MHC-II表位.同样,我们还预测了这些病毒的B细胞线性和不连续包膜蛋白表位.有趣的是,表位在所有三种病毒包膜蛋白中是保守的。Further,不连续表位在结构上与可用的DENV进行比较,ZIKV,WNV,TBEV,和LIV包膜蛋白抗体结构。总体结构比较分析强调(i)E蛋白ED-III结构域中的侧向脊表位,和(ii)包膜二聚体表位(EDE)可以被靶向用于开发有效的疫苗候选物以及治疗性抗体生产。此外,预测同源病毒中相同表位的现有结构和生化功能对黄病毒感染具有降低的抗体依赖性增强(ADE)作用。
BACKGROUND: Flaviviruses cause severe encephalitic or hemorrhagic diseases in humans. Its members, Kyasanur forest disease virus (KFDV) and Alkhumra hemorrhagic fever virus (ALKV), cause hemorrhagic fever and are prevalent in India and Saudi Arabia, respectively, while the tick-borne encephalitis virus (TBEV) causes a dangerous encephalitic infection in Europe and Asia. However, little information is available about the targets of immune responses for these deadly viruses. Here, we predict potential antigenic peptide epitopes of viral envelope protein for inducing a cell-mediated and humoral immune response.
METHODS: Using the Immune Epitope Database and Analysis Resource (IEDB-AR), we identified 13 MHC-I and two MHC-II dominant conserved epitopes in KFDV and ALKV and six MHC-I and three MHC-II epitopes in TBEV envelope proteins. Parallelly, we also predicted B-cell linear and discontinuous envelope protein epitopes for these viruses. Interestingly, the epitopes are conserved in all three viral envelope proteins. Further, the discontinuous epitopes are structurally compared with the available DENV, ZIKV, WNV, TBEV, and LIV envelope protein antibody structures. Overall structural comparison analyses highlight (i) lateral ridge epitope in the ED-III domain of E protein, and (ii) envelope dimer epitope (EDE) could be targeted for developing potent vaccine candidates as well as therapeutic antibody production. Moreover, existing structural and biochemical functions of the same epitopes in homologous viruses are predicted to have a reduced antibody-dependent enhancement (ADE) effect on flaviviral infection.