You may remember HBV, the famous hepatitis virus with its partially double-stranded circular DNA genome. I always wondered: What is that supposed to mean?! HBV has a very complicated replication cycle. I’m pretty sure that all molecular biology fans will be totally thrilled by reading this.

HBV replication cycle is divided into 3 stages:

1- The infectious virion containing the partially double-stranded circular DNA, they call it RC-DNA (relaxed circular).

2- Right after the infection, inside the host nucleus, the genome becomes cccDNA (covalently closed circular DNA). It looks just like plasmids. HBV needs that highly stable form because it’s a chronic infection; it doesn’t want to be lost during host cell division. It may be still there in the host cells even after effective antiviral therapy.

3- Finally transcription takes place, several RNA molecules are produced, some of them are genomic (contain the whole genome) named pgRNA (pregenomic RNA) & some are subgenomic (encode needed enzymes) It uses the cell’s RNA polymerase II to do all this.

So, what happens to the pgRNA? They get inside progeny capsids ready to be reverse transcribed with the help of P protein (Its reverse transcriptase) which is “co-packed” in the pgRNA- progeny capsid package to get it back to the RC-DNA. Then the mature RC-DNA containing-nucleocapsids could undergo cccDNA amplification, or could be enveloped & ready for release from the cell. Of course all this is in equilibrium; if there’s only one copy in the cell, the priority is not to make cccDNA but to be enveloped & released.

Why the RC-DNA needs to be first cccDNA before transcription? As I got from this review, the RC-DNA has the normal (-)-strand (opposite sense to mRNA) but its complementary, the (+)-DNA strand, is not in full length. It results from the non-identical nucleotides supply; because the envelop is impermeable to nucleotides. At the 5′ end of the (-)-strand, there’s the P protein. But at the 5′ end of the (+)-strand, there’s some RNA nucleotides remains from the pgRNA…It was its primer, remember? All these are removed to be a cccDNA. The P protein may has a role in completing the (+)-strand.

Image credits:
Hepatitis B Virus Replication: http://www.meds.com/