Mark Lester C Galicia, Dale Jonathan M Morales, Precious Grace B Pogado, Ashley L Quebrado, Leana Rich Herrera-Ong
{"title":"Identification of potential CD8+ epitopes in pp62 polyprotein of African swine fever virus using computational immunology.","authors":"Mark Lester C Galicia, Dale Jonathan M Morales, Precious Grace B Pogado, Ashley L Quebrado, Leana Rich Herrera-Ong","doi":"10.5114/bta.2023.130726","DOIUrl":null,"url":null,"abstract":"<p><p>The highly infectious African swine fever virus (ASFV) is currently the only known DNA arbovirus within the <i>Asfarviridae</i> 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 <i>in silico</i> 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<sub>50</sub> 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 <i>Sus scrofa domesticus</i> 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 <i>in vitro</i> and <i>in vivo</i> studies in the future.</p>","PeriodicalId":94371,"journal":{"name":"Biotechnologia","volume":"104 3","pages":"221-231"},"PeriodicalIF":0.0000,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/c8/BTA-104-3-51299.PMC10578124.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biotechnologia","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5114/bta.2023.130726","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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.