Bombali virus infection of cynomolgus macaques as a survival model of Ebola virus disease
Ebolaviruses are a genus of emerging RNA viruses of which multiple species are known to cause severe disease and multiple outbreaks in humans. The most recently discovered ebolavirus species, Bombali virus (BOMV), was detected via metagenomic surveillance of bats in Sierra Leone. Additional surveillance detected BOMV in bats from Kenya, Guinea, Mozambique, and Tanzania. Infectious BOMV isolation from field samples has been unsuccessful; however, a recombinant BOMV (rBOMV) has been recovered via reverse genetics. While rBOMV has been used to challenge IFNAR-/- and humanized mice, it has yet to be characterized in a nonhuman primate (NHP) model, which is the gold-standard model for Ebola virus disease (EVD). We challenged eight macaques were challenged intramuscularly with 1000 PFU of rBOMV. Four macaques survived to the predetermined natural history study endpoint (28 DPI), and four were sacrificed at 7 DPI to characterize the disease pathology. NHPs sacrificed at 7 DPI had clear involvement in target organs of ebolavirus replication. Antigen-positive mononuclear cells were present in multiple tissues including the liver (Kupffer cells), lymph nodes, and adrenal gland. NHPs in the natural history study developed classic signs of EVD including coagulopathy with thrombocytopenia, lymphopenia, neutrophilia, and elevated inflammation markers. Disease signs correlated with viremia with onset at ~7 DPI and resolution by 15-21 DPI. BOMV-challenged NHPs developed a robust adaptive immune response, with strong BOMV-specific IgG and neutralizing titers by study endpoint at 28 DPI. This combination of Ebola-like yet nonlethal disease makes rBOMV challenge of cynomolgus macaques an attractive survival model of EVD. Overall design: RNA-seq of whole blood longitudinally samples from cynomolgus macaques challenged with recombinant Bombali virus