title: Computer simulations of proteolysis of Marburg and Ebola-Zaire filovirus coded proteins to generate nonapeptides with motifs of known HLA class I haplotypes and detection of antigenic domains in the viral glycoproteins.
abstract: The primary amino acid sequences of the proteins coded by Marburg and Ebola-Zaire filoviruses were studied by computer programs to search for putative proteolytic cleavages which yield nonapeptides with motifs of binding to known HLA class I haplotypes. The computer analyses predicted that numerous nonapeptides with motifs to bind HLA class I A68 and A2 haplotypes were detected. A few nonapeptides with motifs HLA class I A24, B8, B27 and B35 were predicted in Marburg virus proteins. A similar finding is reported for Ebola-Zaire viral proteins (the viral polymerase was not studied). The search for antigenic domains that may induce the humoral immune response in the viral glycoproteins was based on computer analyses of the physical properties and antigenicity predictions of amino acids in certain domains of the primary amino acid sequences. Twelve putative antigenic domains were detected in Marburg virus glycoprotein and 11 putative antigenic domains in Ebola-Zaire virus glycoprotein. Despite the marked differences in the primary amino acid sequences in the putative antigenic domains of the two viral glycoproteins, 8 antigenic domains were found to have similar locations in the viral glycoproteins of the two viruses. Each pair of antigenic domains resemble each other in the physical properties of the amino acids that are different. These computer analyses may provide an approach to developing synthetic peptides capable of induction of both the cellular and humoral responses to protect against infection with Marburg or Ebola viruses.
authors.affiliation: Department of Molecular Virology, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Becker
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D029043:Ebolavirus / Q000276:immunology*; D010450:Endopeptidases / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology; D000882:Haplorhini; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D029024:Marburgvirus / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D014764:Viral Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D014764:Viral Proteins; D010450:Endopeptidases