Epitope Peptide-Based Predication and Other Functional Regions of Antigenic F and HN Proteins of Waterfowl and Poultry Avian Avulavirus Serotype-1 Isolates From Uganda
Uganda is a Newcastle disease (ND) endemic country where the disease is controlled by vaccination using live LaSota (genotype II) and I2 (genotype I) vaccine strains. Resurgent outbreak episodes call for an urgent need to understand the antigenic diversity of circulating wild Avian Avulavirus seroty...
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Frontiers Media S.A.
2021-06-01
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author | John Bosco Omony John Bosco Omony Agnes Wanyana Kizito K. Mugimba Halid Kirunda Jessica L. Nakavuma Maxwell Otim-Onapa Denis K. Byarugaba |
author_facet | John Bosco Omony John Bosco Omony Agnes Wanyana Kizito K. Mugimba Halid Kirunda Jessica L. Nakavuma Maxwell Otim-Onapa Denis K. Byarugaba |
author_sort | John Bosco Omony |
collection | DOAJ |
description | Uganda is a Newcastle disease (ND) endemic country where the disease is controlled by vaccination using live LaSota (genotype II) and I2 (genotype I) vaccine strains. Resurgent outbreak episodes call for an urgent need to understand the antigenic diversity of circulating wild Avian Avulavirus serotype-1 (AAvV-1) strains. High mutation rates and the continuous emergence of genetic and antigenic variants that evade immunity make non-segmented RNA viruses difficult to control. Antigenic and functional analysis of the key viral surface proteins is a crucial step in understanding the antigen diversity between vaccine lineages and the endemic wild ND viruses in Uganda and designing ND peptide vaccines. In this study, we used computational analysis, phylogenetic characterization, and structural modeling to detect evolutionary forces affecting the predicted immune-dominant fusion (F) and hemagglutinin-neuraminidase (HN) proteins of AAvV-1 isolates from waterfowl and poultry in Uganda compared with that in LaSota vaccine strain. Our findings indicate that mutational amino acid variations at the F protein in LaSota strain, 25 poultry wild-type and 30 waterfowl wild-type isolates were distributed at regions including the functional domains of B-cell epitopes or N-glycosylation sites, cleavage site, fusion site that account for strain variations. Similarly, conserved regions of HN protein in 25 Ugandan domestic fowl isolates and the representative vaccine strain varied at the flanking regions and potential linear B-cell epitope. The fusion sites, signal peptides, cleavage sites, transmembrane domains, potential B-cell epitopes, and other specific regions of the two protein types in vaccine and wild viruses varied considerably at structure by effective online epitope prediction programs. Cleavage site of the waterfowl isolates had a typical avirulent motif of 111GGRQGR'L117 with the exception of one isolate which showed a virulent motif of 111GGRQKR'F117. All the poultry isolates showed the 111GRRQKR'F117 motif corresponding to virulent strains. Amino acid sequence variations in both HN and F proteins of AAvV-1 isolates from poultry, waterfowl, and vaccine strain were distributed over the length of the proteins with no detectable pattern, but using the experimentally derived 3D structure data revealed key-mapped mutations on the surfaces of the predicted conformational epitopes encompassing the experimental major neutralizing epitopes. The phylogenic tree constructed using the full F gene and partial F gene sequences of the isolates from poultry and waterfowl respectively, showed that Ugandan ND aquatic bird and poultry isolates share some functional amino acids in F sequences yet do remain unique at structure and the B-cell epitopes. Recombination analyses showed that the C-terminus and the rest of the F gene in poultry isolates originated from prevalent velogenic strains. Altogether, these could provide rationale for antigenic diversity in wild ND isolates of Uganda compared with the current ND vaccine strains. |
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spelling | doaj.art-fddccb18dcae47f8847ea202aee5af0d2022-12-21T19:19:45ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692021-06-01810.3389/fvets.2021.610375610375Epitope Peptide-Based Predication and Other Functional Regions of Antigenic F and HN Proteins of Waterfowl and Poultry Avian Avulavirus Serotype-1 Isolates From UgandaJohn Bosco Omony0John Bosco Omony1Agnes Wanyana2Kizito K. Mugimba3Halid Kirunda4Jessica L. Nakavuma5Maxwell Otim-Onapa6Denis K. Byarugaba7Department of Microbiology and Biotechnology, Uganda Industrial Research Institute, Kampala, UgandaCollege of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, UgandaCollege of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, UgandaCollege of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, UgandaMbarara Zonal Agricultural Research and Development Institute, National Agricultural Research Organization, Mbarara, UgandaCollege of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, UgandaDirectorate of Science, Research and Innovation, Ministry of Science, Technology and Innovation, Kampala, UgandaCollege of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, UgandaUganda is a Newcastle disease (ND) endemic country where the disease is controlled by vaccination using live LaSota (genotype II) and I2 (genotype I) vaccine strains. Resurgent outbreak episodes call for an urgent need to understand the antigenic diversity of circulating wild Avian Avulavirus serotype-1 (AAvV-1) strains. High mutation rates and the continuous emergence of genetic and antigenic variants that evade immunity make non-segmented RNA viruses difficult to control. Antigenic and functional analysis of the key viral surface proteins is a crucial step in understanding the antigen diversity between vaccine lineages and the endemic wild ND viruses in Uganda and designing ND peptide vaccines. In this study, we used computational analysis, phylogenetic characterization, and structural modeling to detect evolutionary forces affecting the predicted immune-dominant fusion (F) and hemagglutinin-neuraminidase (HN) proteins of AAvV-1 isolates from waterfowl and poultry in Uganda compared with that in LaSota vaccine strain. Our findings indicate that mutational amino acid variations at the F protein in LaSota strain, 25 poultry wild-type and 30 waterfowl wild-type isolates were distributed at regions including the functional domains of B-cell epitopes or N-glycosylation sites, cleavage site, fusion site that account for strain variations. Similarly, conserved regions of HN protein in 25 Ugandan domestic fowl isolates and the representative vaccine strain varied at the flanking regions and potential linear B-cell epitope. The fusion sites, signal peptides, cleavage sites, transmembrane domains, potential B-cell epitopes, and other specific regions of the two protein types in vaccine and wild viruses varied considerably at structure by effective online epitope prediction programs. Cleavage site of the waterfowl isolates had a typical avirulent motif of 111GGRQGR'L117 with the exception of one isolate which showed a virulent motif of 111GGRQKR'F117. All the poultry isolates showed the 111GRRQKR'F117 motif corresponding to virulent strains. Amino acid sequence variations in both HN and F proteins of AAvV-1 isolates from poultry, waterfowl, and vaccine strain were distributed over the length of the proteins with no detectable pattern, but using the experimentally derived 3D structure data revealed key-mapped mutations on the surfaces of the predicted conformational epitopes encompassing the experimental major neutralizing epitopes. The phylogenic tree constructed using the full F gene and partial F gene sequences of the isolates from poultry and waterfowl respectively, showed that Ugandan ND aquatic bird and poultry isolates share some functional amino acids in F sequences yet do remain unique at structure and the B-cell epitopes. Recombination analyses showed that the C-terminus and the rest of the F gene in poultry isolates originated from prevalent velogenic strains. Altogether, these could provide rationale for antigenic diversity in wild ND isolates of Uganda compared with the current ND vaccine strains.https://www.frontiersin.org/articles/10.3389/fvets.2021.610375/fullAvian Avulavirus serotype-1genotype-matched vaccineB-cell epitopesUgandaNewcastle disease |
spellingShingle | John Bosco Omony John Bosco Omony Agnes Wanyana Kizito K. Mugimba Halid Kirunda Jessica L. Nakavuma Maxwell Otim-Onapa Denis K. Byarugaba Epitope Peptide-Based Predication and Other Functional Regions of Antigenic F and HN Proteins of Waterfowl and Poultry Avian Avulavirus Serotype-1 Isolates From Uganda Frontiers in Veterinary Science Avian Avulavirus serotype-1 genotype-matched vaccine B-cell epitopes Uganda Newcastle disease |
title | Epitope Peptide-Based Predication and Other Functional Regions of Antigenic F and HN Proteins of Waterfowl and Poultry Avian Avulavirus Serotype-1 Isolates From Uganda |
title_full | Epitope Peptide-Based Predication and Other Functional Regions of Antigenic F and HN Proteins of Waterfowl and Poultry Avian Avulavirus Serotype-1 Isolates From Uganda |
title_fullStr | Epitope Peptide-Based Predication and Other Functional Regions of Antigenic F and HN Proteins of Waterfowl and Poultry Avian Avulavirus Serotype-1 Isolates From Uganda |
title_full_unstemmed | Epitope Peptide-Based Predication and Other Functional Regions of Antigenic F and HN Proteins of Waterfowl and Poultry Avian Avulavirus Serotype-1 Isolates From Uganda |
title_short | Epitope Peptide-Based Predication and Other Functional Regions of Antigenic F and HN Proteins of Waterfowl and Poultry Avian Avulavirus Serotype-1 Isolates From Uganda |
title_sort | epitope peptide based predication and other functional regions of antigenic f and hn proteins of waterfowl and poultry avian avulavirus serotype 1 isolates from uganda |
topic | Avian Avulavirus serotype-1 genotype-matched vaccine B-cell epitopes Uganda Newcastle disease |
url | https://www.frontiersin.org/articles/10.3389/fvets.2021.610375/full |
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