Unraveling human, rodent and snakeKolmioviridaereplication to anticipate cross-species transmission

Abstract

The recent discovery of Hepatitis D (HDV)-likeviruses across a wide range of taxa led to the establishment of theKolmioviridaefamily. Recent studies suggest that kolmiovirids can be satellites of viruses other than Hepatitis B virus (HBV), challenging the strict HBV/HDV-association dogma. Studying whether kolmiovirids are able to replicate in any animal cell they enter is essential to assess their zoonotic potential. Here, we compared replication of three kolmiovirids: HDV, rodent (RDeV) and snake deltavirus (SDeV)in vitroandin vivo. We show that SDeV has the narrowest and RDeV the broadest host cell range. High resolution imaging of infected cells revealed nuclear viral hubs with a peculiar RNA-protein organization. Finally,in vivohydrodynamic delivery of infectious clones showed that both HDV and RDeV, but not SDeV, efficiently replicate in mouse liver, forming massive nuclear viral hubs. Our comparative analysis lays the foundation for the discovery of specific host factors controllingKolmioviridaehost-shifting.