The hepatitis delta virus RNA genome interacts with the human RNA polymerases I and III

The hepatitis delta virus (HDV) relies on human transcriptional machinery for its replication and transcription. Although the involvement of RNA polymerase II in HDV RNA biosynthesis is established, the contribution of additional polymerases remains uncertain. Here, we demonstrate the interaction of both RNA polymerase I and III with HDV RNA, both in vitro and in human cells. Binding of these polymerases occurs near the terminal stem-loop domains of both polarities of the HDV RNA genome. Based on interactions of HDV RNA with numerous host polymerases, our results suggest a higher level of complexity of HDV biology than previously envisioned.