Discontinuous EBOV RNA synthesis events in patients with Ebola virus disease and their relationship to viral load and outcome of infection

Abstract

EBOV and filoviruses in general are high consequence infectious diseases whose outbreaks can severely impact the lives of those affected. In this study, we show that during EBOV replication in humans, defective genomes can be produced, which complements previous studies in nonhuman primate models of disease and in cell culture. The abundance of these defective genomes correlates with disease outcome in acutely ill patients. In people who go on to die from EVD, they appear to have higher levels of defective genomes than in people who go on to survive infection. This may, in turn, cause a greater upregulation of interferon and inflammation, which are some of the biggest factors in determining disease severity and adverse patient outcome. Therefore, we caution the potential use of defective genomes as a therapy for EVD, as has been proposed for other negative strand RNA viruses.