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Pathogen Page

Ebola virus

I. General Information

1. NCBI Taxonomy ID:

205488

2. Disease:

Ebola hemorrhagic fever

3. Introduction

Ebola virus is an aggressive pathogen that causes a highly lethal hemorrhagic fever syndrome in humans and nonhuman primates. Typically, Ebola virus infection runs its course within 14 to 21 days. Infection initially presents with nonspecific flu-like symptoms such as fever, myalgia, and malaise. As the infection progresses, patients exhibit severe bleeding and coagulation abnormalities, including gastrointestinal bleeding, rash, and a range of hematological irregularities, such as lymphopenia and neutrophilia. Cytokines are released when reticuloendothelial cells encounter virus, which can contribute to exaggerated inflammatory responses that are not protective. Damage to the liver, combined with massive viremia, leads to disseminated intravascular coagulopathy. The virus eventually infects microvascular endothelial cells and compromises vascular integrity. The terminal stages of Ebola virus infection usually include diffuse bleeding, and hypotensive shock accounts for many Ebola virus fatalities (Sullivan et al., 2003).

The Ebola virus genome is 19 kb long, with seven open reading frames encoding structural proteins, including the virion envelope glycoprotein (GP), nucleoprotein (NP), and matrix proteins VP24 and VP40; nonstructural proteins, including VP30 and VP35; and the viral polymerase. The GP open reading frame of Ebola virus gives rise to two gene products, a soluble 60- to 70-kDa protein (sGP) and a full-length 150- to 170-kDa protein (GP) that inserts into the viral membrane through transcriptional editing (Sullivan et al., 2003).

4. Microbial Pathogenesis

Mononuclear phagocytes are the first targets of infection relevant to disease pathogenesis, followed by connective tissues and parenchymal cells. Cytokines are released when reticuloendothelial cells encounter virus, which can contribute to exaggerated nonprotective inflammatory responses. Ebola virus GP plays a vital role in infection. Virual GP appears to form a trimeric complex and binds preferentially to endothelial cells Infection of endothelial cells also induces a cytopathic effect and damage to the endothelial barrier that, together with cytokine effects, leads to the loss of vascular integrity. Cytokine dysregulation and virus infection may synergize at the endothelial surface, promoting hemorrhage and vasomotor collapse. Severity of infection is influenced by age, immune status, and viral virulence. Infection with species-adapted viruses may be lethal. The amount and location of fibin deposits varies with animal species. Strains show differing levels of virulence both across species and by route of administration. Microvascular damage and activation of the clotting cascade occurs. Death is secondary to massive cell death, fluid shifts, hemorrhages, and vascular abnormalities (Sullivan et al., 2003a).

Link to pathogenesis of Ebola virus in HazARD.

5. Host Ranges and Animal Models

The natural host for Ebola virus is unknown (Sullivan et al., 2003).

6. Host Protective Immunity

Both adaptive and innate inflammatory systems respond to infection (Sullivan et al., 2003a). Although antibody titres correlate with the protective response, many studies in non-human primates have suggested that the passive transfer of antibody is insufficient to provide long-lasting protection against Ebola virus (Sullivan et al., 2003b). In rodent studies with adapted Ebola virus, passive transfer of antibodies or adoptive transfer of cytotoxic T cells showed protection when given before infection. A more sensitive but less quantitative CD4 lympho-proliferative response correlated with protection in a DNA/ADV prime–boost study. In addition to the antibody response induced by an effective vaccine, both CD4 and CD8 responses were observed after the challenge. The fact that CD4 responses were not observed before challenge whereas CD8 responses were more consistently seen beforehand suggests that the CD8 response is likely to have an important role in protection in non-human primates (Sullivan et al., 2003b).

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