Early Control Of Viral Load By Favipiravir Promotes Survival To Ebola Virus Challenge And Prevents Cytokine Storm In Non-Human Primates

Author summaryEbola virus was responsible for several epidemics in the recent years and is now considered as a major public health concern in Central and West African countries. We and others demonstrated that pathogenic events observed during Ebola virus disease are linked to a deleterious immune response. However, the mechanisms implicated are not fully understood. Here, we studied immune responses depending on the viral loads observed in infected cynomolgus monkeys. An antiviral treatment allowed the reduction of viral load in some animals and we observed that these animals did not experience deleterious immune response and the loss of hemostasis. The release of pathogen-associated molecular patterns may thus be limited by the inhibition of viral replication, avoiding the overstimulation of the immune system and consequently the pathogenic events observed in Ebola virus disease.Ebola virus has been responsible for two major epidemics over the last several years and there has been a strong effort to find potential treatments that can improve the disease outcome. Antiviral favipiravir was thus tested on non-human primates infected with Ebola virus. Half of the treated animals survived the Ebola virus challenge, whereas the infection was fully lethal for the untreated ones. Moreover, the treated animals that did not survive died later than the controls. We evaluated the hematological, virological, biochemical, and immunological parameters of the animals and performed proteomic analysis at various timepoints of the disease. The viral load strongly correlated with dysregulation of the biological functions involved in pathogenesis, notably the inflammatory response, hemostatic functions, and response to stress. Thus, the management of viral replication in Ebola virus disease is of crucial importance in preventing the immunopathogenic disorders and septic-like shock syndrome generally observed in Ebola virus-infected patients.