In general, Ebola viruses are well known for their ability to cause severe hemorrhagic
fever in both human and nonhuman primates. However, despite substantial sequence homology to other members of the family Filoviridae,
Reston ebolavirus displays reduced pathogenicity for nonhuman primates and has never been demonstrated to cause clinical disease in humans, despite its ability to cause
infection. In order to develop a tool to explore potential roles for transcription and replication in the reduced pathogenicity of
Reston ebolavirus, we developed an
RNA polymerase I (Pol I)-driven minigenome system. Here we demonstrate successful
Reston ebolavirus minigenome rescue, including encapsidation, transcription, and replication, as well as the packaging of minigenome transcripts into progeny particles. The Pol I-driven
Reston ebolavirus minigenome system provides a higher signal intensity with less background (higher signal-to-noise ratio) than a comparable T7-driven
Reston ebolavirus minigenome system which was developed simultaneously. Successful
Reston ebolavirus minigenome rescue was also achieved by the use of helper plasmids derived from the closely related Zaire ebolavirus or the more distantly related Lake Victoria marburgvirus. The use of heterologous helper plasmids in the
Reston ebolavirus minigenome system yielded levels of reporter expression which far exceeded the level produced by the homologous helper plasmids. This comparison between minigenomes and helper plasmids from different filovirus species and genera indicates that inherent differences in the transcription and/or replication capacities of the
ribonucleoprotein complexes of pathogenic and apathogenic filoviruses may exist, as these observations were confirmed in a Lake Victoria marburgvirus minigenome system.