Identification of potential CD8+ epitopes in pp62 polyprotein of African swine fever virus using computational immunology.

Biotechnologia Pub Date : 2023-09-25 eCollection Date: 2023-01-01 DOI:10.5114/bta.2023.130726
Mark Lester C Galicia, Dale Jonathan M Morales, Precious Grace B Pogado, Ashley L Quebrado, Leana Rich Herrera-Ong
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Abstract

The highly infectious African swine fever virus (ASFV) is currently the only known DNA arbovirus within the Asfarviridae family which primarily infects domestic pigs and wild boars. African swine fever (ASF) leads to a mortality rate of up to 100% which has caused massive socio-economic losses worldwide. Previous research indicates that ASFV's virulence can be attributed to polyprotein pp62, which plays a crucial role in viral assembly and core maturation. This particular study utilized in silico analysis to identify highly conserved cytotoxic T-cell epitopes in pp62 that can potentially serve as key components for future ASFV vaccines. To achieve this, the researchers retrieved, clustered, and aligned the peptide sequences of pp62. Subsequently, the aligned sequences were analyzed to identify epitopes that bind promiscuously to the swine major histocompatibility complex I (MHC I) alleles and exhibiting MHC IC50 values < 500 nM. Additionally, peptide sequences with positive proteasome and TAP scores were considered. Potential cross-reactivity was assessed by comparing the peptide sequences against available proteome sequences of Sus scrofa domesticus in various databases. Furthermore, molecular docking was conducted to evaluate the binding of candidate epitopes with swine leukocyte antigen-1*0401 (SLA-1*0401). The dissociation constants, binding energies, root mean square deviation, and root mean square fluctuation values for the SLA-epitope complexes were compared with a positive reference. In the course of the study, 21 highly conserved CD8+ epitopes were identified, out of which four were further assessed for their potential immunogenicity. The results demonstrated that the highly conserved CD8+ epitopes discovered in this study are promising for integration into future ASFV vaccine formulations. As preliminary data, it is anticipated that these findings will subsequently undergo in vitro and in vivo studies in the future.

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使用计算免疫学鉴定非洲猪瘟病毒pp62多蛋白中潜在的CD8+表位。
传染性极强的非洲猪瘟病毒(ASFV)是目前已知的唯一一种主要感染家猪和野猪的阿氏病毒科DNA虫媒病毒。非洲猪瘟的死亡率高达100%,在全球范围内造成了巨大的社会经济损失。先前的研究表明,ASFV的毒力可归因于多蛋白pp62,它在病毒组装和核心成熟中起着至关重要的作用。这项特殊的研究利用计算机分析来鉴定pp62中高度保守的细胞毒性T细胞表位,这些表位可能成为未来ASFV疫苗的关键成分。为了实现这一点,研究人员对pp62的肽序列进行了检索、聚类和比对。随后,对比对的序列进行分析,以鉴定与猪主要组织相容性复合体I(MHC I)等位基因混杂结合并显示MHC IC50值<500nM的表位。此外,还考虑了蛋白酶体和TAP评分为阳性的肽序列。通过将肽序列与各种数据库中Sus scrofa domesticus的可用蛋白质组序列进行比较来评估潜在的交叉反应性。此外,进行分子对接以评估候选表位与猪白细胞抗原-1*0401(SLA-1*0401)的结合。将SLA表位复合物的解离常数、结合能、均方根偏差和均方根波动值与阳性参考进行比较。在研究过程中,鉴定了21个高度保守的CD8+表位,其中4个表位的潜在免疫原性得到了进一步评估。结果表明,本研究中发现的高度保守的CD8+表位有望整合到未来的ASFV疫苗配方中。作为初步数据,预计这些发现将在未来进行体外和体内研究。
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