Elucidation of the molecular basis of negative-strand RNA virus genome replication

The negative-strand RNA viruses are a group that includes many important pathogens. They share the common mechanism of genome replication and mRNA transcription. The viruses possess multifunctional RNA-dependent RNA polymerase that is responsible for all RNA synthesis activity, and the genome RNA is entirely covered with viral nucleoprotein. We aimed to understand these viruses in general by identifying the similarities and differences among each virus group. The viruses belonging to the family Paramyxoviridae in the order Mononegavirales is known to follow the "Rule of Six", which states that the number of nucleotides in the genome must be a multiple of six to be replicated. We have succeeded in generating a paramyxovirus that does not follow the Rule of Six and challenged to elucidate the significance of the Rule of Six using this recombinant virus. We also performed functional analysis of the promoter structure at the end of the genome of the viruses belonging to the order Bunyavirales and revealed unique features of RNA synthesis that differ from other segmented RNA viruses in the family Nairoviridae. Furthermore, we elucidated the unique mechanism of the Borna disease virus to establish persistent infection in the nucleus that is an exceptional property among RNA viruses.