Pathogenesis and natural history of the Bundibugyo species of Orthoebolavirus in nonhuman primates

The current outbreak of Bundibugyo virus (BDBV) in Africa poses a significant global public health concern, given the absence of licensed medical countermeasures (MCM). To address this issue, researchers exposed 21 cynomolgus monkeys (CM) to BDBV to study the progression and natural history of BDBV disease (BVD). The findings reveal that BVD in CM is more protracted compared to other infections like Ebola and Sudan, with a lower lethality rate of 67%, which aligns with the lower human BVD mortality rates observed.

Through the use of IHC and spatial proteomics, researchers identified macrophages and dendritic cells as early targets of BDBV infection. These infected cells often colocalized with fibrin and infiltrating MPO+ neutrophils and S100A9+ myeloid-derived suppressor cells, indicating the development of an active inflammatory response and early coagulopathy.

The study also revealed that transcriptomic and proteomic analyses of the circulating immune response in CM reflected a cytokine-driven hyperinflammatory state succumbing to disease upon exposure to BDBV.

Despite surviving the initial infection, some animals continued to show signs of systemic inflammation by the study's endpoint. However, BDBV antigen was detected in immune privileged tissues, accompanied by lesion-associated inflammation that parallels known post-Ebola sequelae in humans. This research provides valuable insights into the disease course of BDBV, highlighting potential weaknesses that can be targeted to develop new medical countermeasures.