Hepatitis B Virus Genotype G forms core-like particles with unique structural properties

SUMMARY: We have determined the structure of the core capsid of an unusual variant of hepatitis B virus, genotype G (HBV/G) at 14 Å resolution, using cryo-electron microscopy. The structure reveals surface features not present in the prototype HBV/A genotype. HBV/G is novel in that it has a unique 36- bp insertion downstream of the core gene start codon. This results in a twelve amino acid insertion at the N-terminal end of the core protein, and two stop codons in the precore region that prevent the expression of HBeAg. HBV/G replication in patients is associated with co-infection with another genotype of HBV, suggesting that HBV/G may have reduced replication efficiency in vivo. We localized the N-terminal insertion in HBV/G and show that it forms two additional masses on the core surface adjacent to each of the dimer-spikes and have modelled the structure of the additional residues within this density. We show that the position of the insertion would not interfere with translocation of nucleic acids through the pores to the core interior compartment. However, the insertion may partially obscure several residues on the core surface that are known to play a role in envelopment and secretion of virions, or that could affect structural rearrangements that may trigger envelopment after DNA second-strand synthesis.