The HDV virion is a spherical particle of about 36-nm in diameter, which contains an envelope with HBsAg and a nucleocapsid containing an RNA genome in complex with HDAg [7,8]. Genomic HDV RNA is approximately 1.7 kb in length and consists of a single-stranded, circular RNA of negative polarity, with a high degree of intra-molecular base paring that allows it to fold into an unbranched rod-like structure under the native condition [9,10] (Figure 1). Albeit the fact that HDV RNA is three to four times longer than plant viroids, the semi-double-strand structure of HDV RNA is very similar to that adopted by viroid RNAs. The extra sequence of HDV RNA contains an open reading frame (ORF) which is responsible for the coding of HDAg on the complementary strand (antigenomic RNA). HDV also contains ribozyme domains on both the genomic and antigenomic strands, which are required for the cleavage of the respective RNA strands in cis during RNA replication [11,12] (Figure 1). This is another feature shared between HDV RNA and some plant viroids.