Comparison of Ebola virus infection routes and resulting disease in animal models

Ebola virus disease (EVD) is a highly pathogenic and lethal disease caused by Ebola virus (EBOV). Endemic to Sub-Saharan Africa, EBOV has been causing global health concerns during infrequent EVD outbreaks since 1976, particularly during the 2013 -2016 epidemic in West Africa. Spread by contact of contaminated bodily fluids with mucous membranes or breaks in the skin, EBOV yields an incredibly high mortality rate and, as a result, has been designated a priority pathogen and a select agent to be studied exclusively in maximum containment laboratories. EBOV has historically been studied in animal models that accurately recapitulate disease progression, symptoms, and outcomes as seen in humans via more artificial infection routes such as intramuscular (IM) and intraperitoneal (IP) inoculation. There has recently been a concerted effort to characterize disease in animal models with mucosal inoculation routes with the goal to more accurately replicate human infection and development of EVD. This review aims to summarize and characterize the different inoculation routes used in the various animal models applied in EBOV research. We also outline the differences in disease progression between "artificial" and mucosal infection routes, comparing them to the course of EVD as seen in humans to highlight similarities and differences.