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利用计算免疫学鉴定非洲猪瘟病毒pp62多聚蛋白中潜在的CD8 +表位

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

作者信息

Galicia Mark Lester C, Morales Dale Jonathan M, Pogado Precious Grace B, Quebrado Ashley L, Herrera-Ong Leana Rich

机构信息

Department of Physical Sciences, College of Science, Polytechnic University of the Philippines, Manila, Philippines.

Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines, Manila, Philippines.

出版信息

BioTechnologia (Pozn). 2023 Sep 25;104(3):221-231. doi: 10.5114/bta.2023.130726. eCollection 2023.

Abstract

The highly infectious African swine fever virus (ASFV) is currently the only known DNA arbovirus within the 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 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 IC 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 in various databases. Furthermore, molecular docking was conducted to evaluate the binding of candidate epitopes with swine leukocyte antigen-10401 (SLA-10401). 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 and studies in the future.

摘要

高传染性的非洲猪瘟病毒(ASFV)是目前该病毒科中唯一已知的DNA虫媒病毒,主要感染家猪和野猪。非洲猪瘟(ASF)导致的死亡率高达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的毒力可归因于多聚蛋白pp62,它在病毒组装和核心成熟过程中起着关键作用。这项具体研究利用分析来确定pp62中高度保守的细胞毒性T细胞表位,这些表位有可能成为未来ASFV疫苗的关键组成部分。为实现这一目标,研究人员检索、聚类并比对了pp62的肽序列。随后,对比对后的序列进行分析,以确定能与猪主要组织相容性复合体I(MHC I)等位基因广泛结合且MHC I C值<500 nM的表位。此外,还考虑了蛋白酶体和转运相关蛋白(TAP)评分呈阳性的肽序列。通过将肽序列与各数据库中可用的蛋白质组序列进行比较来评估潜在的交叉反应性。此外,进行了分子对接以评估候选表位与猪白细胞抗原-10401(SLA-10401)的结合情况。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对照进行比较。在研究过程中,鉴定出了21个高度保守的CD8+表位,其中4个进一步评估了其潜在免疫原性。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,预计这些发现随后将在未来进行[此处原文缺失两个词]和[此处原文缺失两个词]研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d185/10578124/1e5a612771af/BTA-104-3-51299-g001.jpg

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