Characterization of a cis element required for packaging and replication of the human hepatitis B virus

The hepatitis B virus (HBV) is a DNA virus; however, it replicates through a pregenomic RNA intermediate. Several HBV-specific mRNAs are transcribed, but only the pregenomic RNA transcript is encapsidated. The encapsidation of the HBV genome, therefore, is a highly specific and selective process. Using mutational analyses and complementation tests, we have defined a 99-nucleotide cis element located at the pre-C/C region of the HBV genome which is essential for encapsidation and the replication. Furthermore, HBV genome truncated down to 1.5 kb and HBV mutants carrying foreign DNA inserts could still replicate in our complementation system.