DNA synthesis inside the hepatitis B virus creates a high-energy spool

Abstract

The Hepatitis B Virus (HBV) capsid assembles around an RNA pregenome which is reverse-transcribed into double-stranded DNA. It remains unclear how this DNA, which is stiff, bulky, and has significant negative charge, is accommodated within the capsid. The organization of the genome will answer this and lend insight into the viral reverse transcription reaction. We determined the structures of mature HBV and Duck HBV, finding that the DNA forms a spool that is coaxial with the capsids fivefold symmetry and interacts with charges on the capsid interior. We calculate that the energy of DNA bending would create a metastable capsid that just awaits a trigger for DNA release. Thus, we see how nature has created a fragile energy minimum that enables genome uncoating.