A Chimeric Lloviu Virus Minigenome System Reveals that the Bat-Derived Filovirus Replicates More Similarly to Ebolaviruses than Marburgviruses

Abstract

Summary: Recently, traces of zoonotic viruses have been discovered in bats and other species around the world, but despite repeated attempts, full viral genomes have not been rescued. The absence of critical genetic sequences from these viruses and the difficulties to isolate infectious virus from specimens prevent research on their pathogenic potential for humans. One example of these zoonotic pathogens is Lloviu virus (LLOV), a filovirus that is closely related to Ebola virus. Here, we established LLOV minigenome systems based on sequence complementation from other filoviruses. Our results show that the LLOV replication and transcription mechanisms are, in general, more similar to ebolaviruses than to marburgviruses. We also show that a single nucleotide at the 3′ genome end determines species specificity of the LLOV polymerase. The data obtained here will be instrumental for the rescue of infectious LLOV clones for pathogenesis studies. : Lloviu virus (LLOV) is a filovirus of unknown pathogenicity, and the viral genome ends have not been recovered. Manhart et al. established a minigenome system for studying LLOV by complementing missing sequence information with that of other filoviruses. This minigenome provides a blueprint for generating recombinant LLOV for pathogenesis studies. Keywords: Lloviu virus, filoviruses, Ebola virus, Marburg virus, minigenomes, replication and transcription, RNA-dependent RNA polymerase, emerging viruses