Hepatitis B X gene 5' end at different clinical stages: comparing conservation/variability and quasispecies complexity

To explore the fragment of hepatitis B virus (HBV) genome containing the 5'-end of the hepatitis B X gene (HBX) transcripts, from nucleotides (nt) 1255 to 1611. We assessed the conservation and variability of this region to detect hyper-conserved regions, regardless of the clinical stage or HBV genotype of chronic HBV infection, by calculation of the Information Content (IC) of each nt position in a multiple alignment of all sequences obtained by Next-Generation Sequencing. The fragment of HBV genome containing the 5' end of HBX transcripts presented hyper-conserved regions independently of the clinical stage of patients and the HBV genotype. Despite these hyper-conserved regions, we also identified patterns of mutations associated to both clinical stage and viral genotype. Moreover, we characterized the quasispecies complexity in the same groups of patients where we studied the variability, and also in chronic hepatitis D virus (HDV) co-infected patients. Interestingly the groups with lower HBV replication showed a higher quasispecies complexity.