Abstracts

Human Genome Diversity

The structural bases of hemorrhagic and connective tissue complications of Ebola virus infection are poorly understood. To approach the problem, we developed a novel algorithm searching for local homologies between viral and human proteins, which is based on specially designed matrix reflecting the effect of amino acid substitutions on protein-protein interaction.

Early we have developed at Vector the strain 8mc of Ebola virus, which is highly pathogenic for guinea pigs (Chepurnov et al., 1995). It has several amino acid differ-ences from the reference strain Zaire-1976, which is nonpathogenic for guinea pigs. We analyzed the regions of Ebola virus proteins that include differences between 8mc and Zaire-1976 strains. Several regions in human proteins associated with vascular en-dothelial cells were found which have a prominent similarity with protein fragments from pathogenic strain of Ebola virus and only a slight one with corresponding regions from nonpathogenic strain. The similarities found are enough for inducting cross-reactive antibodies or CTL or for competitive replacement of human proteins by similar fragments of virus proteins, thereby interfering with the organism homeostasis.

To study this molecular mimicry hypothesis two groups of guinea pigs (5 animals each) were infected with strains Zaire-1976 and 8mc, respectively. Animals from the first group have developed an increasing of rectal temperature by 1-1.5C within 6-15 days after infection with a following recovery. Animals from the second group have developed an increasing of rectal temperature by 2-3C within 4-5 days after infection. All animals from the second group were lost within 7-12 days after infecting. By using sera from animals from these two groups we have demonstrated immunohistochemi-cally that experimental infection of guinea pigs with adapted strain 8mc of Ebola virus is accompanied by production of autoimmune antibodies interacting with host endothelial cells (Figure 1). At the same time experimental infection of guinea pigs with wild strain Zaire-1976 of Ebola virus is not accompanied by production of autoimmune antibodies interacting with host endothelial cells. Interpreting the data obtained we are stating the appearance of autoantibodies in the course of lethal Ebola infection. In our opinion these autoantibodies, which are produced against Ebola virus proteins, cross-react with host endothelial cells because of molecular mimicry.

Note. Abstracts are published in author's edition

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