Ebola Virus Disease in Humans: Pathophysiology and Immunity

Abstract

Viruses of the Ebolavirus genus cause sporadic epidemics of severe and systemic febrile disease that are fueled by human-to-human transmission. Despite the notoriety of ebolaviruses, particularly Ebola virus (EBOV), as prominent viral hemorrhagic fever agents, and the international concern regarding Ebola virus disease (EVD) outbreaks, very little is known about the pathophysiology of EVD in humans and, in particular, about the human immune correlates of survival and immune memory. This lack of basic knowledge about physiological characteristics of EVD is probably attributable to the dearth of clinical and laboratory data gathered from past outbreaks. The unprecedented magnitude of the EVD epidemic that occurred in West Africa from 2013 to 2016 has allowed, for the first time, evaluation of clinical, epidemiological, and immunological parameters in a significant number of patients using state-of-the-art laboratory equipment. This review will summarize the data from the literature regarding human pathophysiologic and immunologic responses to filoviral infection.

Comparative pathogenesis of Ebola virus and Reston virus infection in humanized mice

“…Even though further studies are needed to dissect the pathogenic features of ebolaviruses in huNSG-A2 mice, our initial studies indicate that the susceptibility of these mice to specific ebolaviruses was very similar to that of humans. Moreover, within the Zaire ebolavirus species, huNSG-A2 mice were significantly less susceptible to Makona virus compared with Mayinga virus, which was in agreement with reported CFRs in human (17,21) and animal model studies (25,26).…”

“…Mucosal RESTV replication kinetics is delayed with respect to that of EBOV. The natural portals of entry of ebolaviruses in humans are the skin and the mucosae (17). Therefore, we first evaluated the presence of human mature immune cells in the skin and mucosae of huNSG-A2 mice 12 weeks after transplantation of human CD34 + HSCs.…”

Ebola virus disease

“…of biomarkers of inflammation (such as CCL2, IL-8 and IL-6), endothelial dysfunction (such as selectin P), coagulation (such as d-dimer, tissue factor and von Willebrand factor) and lymphocyte function (such as CXCL3 and granzyme B) 127,128 ; the expression of host RNA transcripts from peripheral blood mononuclear cells; and the appearance of EBOV-specific humoral and cellular immune responses. Data from both patients with EVD treated in the USA and Western African cohorts suggest that robust adaptive immune activation, which includes antigen-specific T cell and B cell responses, occurs during acute illness 123 .…”

Kinetics of Soluble Mediators of the Host Response in Ebola Virus Disease

“…Ebola virus (EBOV) is the prototype filovirus causing Ebola virus disease (EVD), a severe infection characterized by strong inflammation, profound disruption of host immune responses, and a multiorgan syndrome that resembles septic shock [ 1 , 2 ]. One of the most common findings in EVD is an increased level of circulating proinflammatory cytokines, which has been associated to high viral load [ 3 ]. Previous studies have correlated the expression of proinflammatory mediators in plasma from patients with acute EVD to disease severity, thereby pointing out that cytokine expression might be used as a predictor of EVD outcome [ 4–6 ].…”