Keywords: Ebola virus, EBOV, human proteins, Marburg, local similarity, vaccine design, virulence, molecular mimicry, pathogenesis, lethal strains, non-lethal strains, filovirus vaccines, epitopes, hemorrhagic fever, autoimmune reaction
Possible role of molecular mimicry in pathogenesis of Ebola virus: implications for a rational vaccine design
Ebola Virus (EBOV) presents a challenge for vaccine development because immune correlates of protection in humans are not well known. In earlier studies we developed a concept of local similarity which refers to resemblance of structural patterns of unrelated proteins as a function of their amino acid composition. The search for local similarities between human and EBOV proteins was performed. The resemblance of NP protein of EBOV to vascular endothelial growth factor and its receptor, which play a key role in the regulation of vascular permeability, was identified. A high degree of local similarity of Ebola GP protein with the tactile protein of the T-cell surface was also revealed. The similarity of the Ebola VP24 protein fragment with complement receptor type 1 (CD35 antigen) appears to be correlated with early activation of complement in lethal Ebola fever. This finding supports our prior studies indicating that VP24 determines the difference between lethal and non-lethal strains of EBOV. Several other similarities of potential significance were identified that might play an important role in the aetiology of Ebola-induced disease. In conclusion, local similarities between EBOV and human host proteins may provide a key to rational design of safe and effective filovirus vaccines. Such a vaccine must be free from epitopes that could potentially trigger Ebola-like hemorrhagic fever due to an autoimmune reaction induced by vaccination and other unanticipated adversities.