Hepatitis B virus DNA polymerase

The hepadnaviral P protein is organized into three domains: an N-terminal domain (InterPro: IPR000201) covering the terminal and the spacer, an RT domain related to every other RT domain, and a C-terminal domain (InterPro: IPR001462) regulating the RNase H activity.

In HBV the pgRNA, is translated into the viral polymerase and core proteins, and then encapsidated and reverse transcribed to form a new rcDNA molecule. In this stage, the HBV polymerase has some tasks and functions. The HBV polymerase is a multifunctional enzyme with RNA-dependent and DNA-dependent polymerase and RNase H activities.[3] Furthermore, hepadnavirus polymerases contain a terminal protein (TP) domain that contains a tyrosine residue that serves as a primer for the synthesis of the (-) DNA strand.[3]

In reverse transcription steps, existing of HBV core protein dimers is required for packaging of the pgRNA/polymerase complex. Then, after viral polymerase binds to the packaging signal (Hɛ) found at the 5′ end of the pgRNA, they are incorporated into the viral capsid.[3][4] Inside the capsid, the pgRNA undergoes reverse transcription, which is initiated by protein priming at the tyrosine residue of the HBV polymerase. Thus, (-) DNA strand is made.[4] At the same time, degradation of the RNA template is took place by the RNase H activity of the polymerase. A short RNA of about 15–18 nucleotides at the 5′ end of the pgRNA (including the 5′ DR1 sequence) is not degraded and it is used as primer for (+) DNA strand synthesis.[3]

The resulting RC-DNA is partially double stranded. The (-) DNA strand is longer than a genome length, with a covalently bound polymerase and a redundant flap at the 5′ end. However, the (+) DNA strand synthesis is uncompleted by the polymerase, and there is a gap exists down to the 3′ end of the (+) DNA strand.[4]