Development of reverse genetic systems for the novel filovirus Bombali virus for assessment of pathogenicity and possible countermeasures

Recently, a number of novel filoviruses such as Bombali virus (BOMV) have been discovered in diverse bat species. However, no virus isolates were obtained so far, which hinders an assessment of the pathogenic potential of these viruses, which are related to highly pathogenic filoviruses such as Ebola virus (EBOV). To address this issue, we have developed reverse genetic systems for BOMV, including life cycle modelling systems to analyze the biological activity of proteins encoded by the published BOMV sequences. This also allowed us to test the efficacy of remdesivir, a known inhibitor of the EBOV polymerase L, which showed comparable effectivity against BOMV and EBOV. Testing of the published BOMV glycoprotein sequence suggested a putative sequencing error in a highly conserved region, resulting in a non-functional protein. Combining these results with a BOMV full length clone system we generated allowed us to rescue and characterize recombinant BOMV, and we are now in the process of assessing the pathogenic potential of BOMV in a small animal model that reflects differences in the pathogenic potential of different filovirus species in humans. This study demonstrates the potential of reverse genetics systems to analyze the pathogenic potential of viruses with zoonotic potential in the absence of natural isolates, to quickly test potential antivirals, and to better understand their molecular biology.