Capped small RNAs and MOV10 in Human Hepatitis Delta Virus replication

The evolutionary origin of human Hepatitis Delta Virus (HDV) replication by RNA-directed transcription is unclear. Here we identify two species of 5′ capped, ∼18-25 nucleotide small RNAs. One was of antigenomic polarity corresponding to the 5′ end of Hepatitis Delta Antigen (HDAg) mRNA and interacted with HDAg and RNA POLYMERASE II (POL II), while the other mapped to a structurally analogous region on the genomic RNA hairpin. An HDAg-interaction screen uncovered MOV10, the human homologue of the A. thaliana RNA amplification factor SDE3 and D. melanogaster RISC-maturation factor Armitage. MOV10 knockdown inhibited HDV replication, but not HDAg mRNA translation supporting a role for MOV10 in RNA-directed transcription. Together, our studies define RNA hairpins as critical elements for the initiation of HDV-related RNA-directed transcription. The identification of capped small RNAs and the involvement of MOV10 in HDV replication further suggest a conserved mechanism related to RNA-directed transcription in lower eukaryotes.