Immunological Perspective for Ebola Virus Infection and Various Treatment Measures Taken to Fight the Disease

Abstract

Ebolaviruses, discovered in 1976, belongs to the Filoviridae family, which also includes Marburg and Lloviu viruses. They are negative-stranded RNA viruses with six known species identified to date. Ebola virus (EBOV) is a member of Zaire ebolavirus species and can cause the Ebola virus disease (EVD), an emerging zoonotic disease that results in homeostatic imbalance and multi-organ failure. There are three EBOV outbreaks documented in the last six years resulting in significant morbidity (> 32,000 cases) and mortality (> 13,500 deaths). The potential factors contributing to the high infectivity of this virus include multiple entry mechanisms, susceptibility of the host cells, employment of multiple immune evasion mechanisms and rapid person-to-person transmission. EBOV infection leads to cytokine storm, disseminated intravascular coagulation, host T cell apoptosis as well as cell mediated and humoral immune response. In this review, a concise recap of cell types targeted by EBOV and EVD symptoms followed by detailed run-through of host innate and adaptive immune responses, virus-driven regulation and their combined effects contributing to the disease pathogenesis has been presented. At last, the vaccine and drug development initiatives as well as challenges related to the management of infection have been discussed.

Keywords: Ebola vaccines; T-cell immunity; bystander apoptosis; cytokines response; host immune evasion.

Figure 1

A schematic representation of Ebola virus (EBOV) pathogenesis. The virus is capable of productively infecting monocytes, macrophages, dendritic cells (DC) (except epidermal, mucosal and CD141⁺ DC) and hepatocytes. The virus does not enter lymphocytes but can show interaction with CD4⁺ T-cells. Despite non-entry into lymphocytes, bystander lymphocyte apoptosis is observed during the course of infection which could lead to T-cell exhaustion. Infection of hepatocytes could result in downregulation of blood coagulation enzymes which could lead to hemorrhage. Severe infection leads to hyperproduction of proinflammatory cytokines. These cytokines activate coagulation factors such as thrombomodulin, ferritin etc. The released coagulation factors in turn upregulate proinflammatory cytokines, as depicted. Hence, a deadly chain reaction ensues upon filoviral infection which might culminate into shock, vascular damage (disseminated intravascular coagulation which might lead to hemorrhage especially rashes, gastrointestinal and conjunctival hemorrhage in the later stages) and homeostatic imbalance.

Figure 2

Mechanisms of host immune evasion employed by Ebola virus.