Epitope specificity and protein signaling interactions driving epidemic occurrences of Ebola disease

Abstract

Ebolavirus has as main hosts, humans and nonhuman primates where its pathogenic effects result to serious hemorrhagic fever with lethal effects. Despite the great advancement in deciphering the clinical course of the virus, specific mechanisms favoring Ebolavirus pathogenicity and transmission, and which genomic structures are most antigenic, are still to be clearly delineated. This study used functional protein phylogenetic analysis, pathway designs and antigenic epitope predictions to respectively; identify viral genomic regions closely related to host proteins, predict protein/genetic interactions favoring viral pathogenesis and identify frequency of MHC class I & II immune related host peptide variants whose transmission intensity value favors disease epidemicity. Viral glycoprotein (VGP) presented the highest genetic variation and though captured on the network with matrix protein (MXP), no direct interaction was observed. The majority of host interacting proteins presented with kinase functions, particularly a protein-signaling role observed in LCK, a Tyrosine-protein kinase with the most dominant interactions and viral related functions implicated in disease shock events. Four VGP and three MXP main antigenic epitopes identified, differentially showed high frequency to two MHC class I types. The same pattern was observed for VGP and MXP antigenic epitopes predicted to MHC class II allele variants, favoring high transmission intensity values within the host population, suggesting their involvement in Ebola epidemic upsurges. Related Ebola species with high transmission values were dominantly non-Zaire Ebolaviruses whose antigenic regions showed several repeats, implicating them in viral antigenic variations. Our analysis show that VGP and MXP are both critical for viral entry and pathogenicity in the host and with their species specific occurrence, their combined role in drug/vaccine design is critical. The identification of several antigenic epitopes in this study will be used in combination for drug/vaccine design and for better understanding related molecular targets in pathogenic pathways favoring Ebola disease burden.