Pathophysiology of Ebola Virus Infection: Current Challenges and Future Hopes

Abstract

The filoviruses, Ebola virus (EBOV) and Marburg virus (MARV), are among the deadliest viruses that cause disease in humans, with reported case fatality rates of up to 90% in some outbreaks. The high virulence of EBOV and MARV is largely attributed to the ability of these viruses to interfere with the host immune response. Currently, there are no approved vaccines or postexposure therapeutics, and treatment options for patients infected with EBOV are limited to supportive care. In this review, we discuss mechanisms of EBOV pathogenesis and its ability to subvert host immunity as well as several vaccines and therapeutics with respect to their evaluation in small animal models, nonhuman primates, and human clinical trials.

Keywords: Ebola therapeutics; Ebola vaccines; Ebola virus; adaptive immunity; antivirals; immunoevasion; innate immunity; viral hemorrhagic fever.

Figure 1.. Dysregulation of Immune System by Ebola virus.

Monocytes, macrophages, and dendritic cells are preferred sites of filovirus replication. Infection of monocytes and macrophages triggers robust expression of inflammatory mediators. Inflammatory mediators, reactive oxygen species and nitric oxide can induce apoptosis leading to lymphocyte death. Infection of dendritic cells impairs their maturation and suppresses type I (IFN) responses thereby preventing T cell activation. Production of EBOV soluble glycoprotein (sGP) usurps GP-specific antibodies.