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.

Remdesivir is efficacious in rhesus monkeys exposed to aerosolized Ebola virus

“…The only observed changes in the lungs of remdesivir-treated animals were mild congestion and hypertrophy of the germinal centers in the tracheobronchial lymph nodes. These findings are indicative of the immune response to EBOV infection as it is known that EBOV dysregulates immune responses by both immune suppression and activation, although the role of these responses during infection is not completely understood 43 .…”

“…Despite these promising results for antibody-based therapeutics, substantial gaps remain in improving the outcomes of acute EVD, particularly for individuals with severe disease, and for prevention and treatment of viral persistence in immune-privileged sites. The latter may limit the overall utility of both vaccine and antibody-based therapeutic strategies 43 , 44 .…”

Structural and Functional Aspects of Ebola Virus Proteins

“…In December 2019, Ervebo, a recombinant vesicular stomatitis virus (VSV) vector-based vaccine, was approved by FDA as the first vaccine against the Ebola virus [216]. Currently, nearly 14 potent Ebola vaccine candidates are in various phases of clinical trials [217]. Still, the presence of non-immunogenic, unwanted components in traditional vaccines, allergic, toxic, or autoimmune reactions, the requirement for BSL-4 facility and probability of a reversal of attenuated virus state [218][219][220] impede EBOV vaccine development efforts.…”

Conserved immunogenic peptides of Ebola glycoprotein elicit immune response in human peripheral blood mononuclear cells

“…Generally, Ebola survivors seem to mount an effective T-cell mediated viral clearance response despite initial lymphocyte apoptosis. 28 Also, little or no humoral immune response during EVD is suggested to be a credible marker of fatality. 28 Upon persistent interaction with an antigen, lymphocytes undergo proliferation followed by differentiation to generate specialized cells which specifically identify and exterminate the pathogen.…”

“…28 Also, little or no humoral immune response during EVD is suggested to be a credible marker of fatality. 28 Upon persistent interaction with an antigen, lymphocytes undergo proliferation followed by differentiation to generate specialized cells which specifically identify and exterminate the pathogen. Thus, lymphocyte proliferation indicates the initiation of an immune response towards immunogenic peptides.…”