A mutation at nucleotide 1896 (G1896A) is the most common cause for the loss of HBeAg. In contrast to clinical data, cell culture studies report a high-replicating phenotype for the G1896A mutant. Differences between the wild-type and the G1896A mutant in early steps of HBV replication including the synthesis of pre-genomic RNA and transcripts have not been investigated. The G1896A mutant is associated with higher replication fitness, transcription efficiency and higher levels of secreted HBsAg than the wild-type. Interestingly, trans-complementation of the G1896A mutant with HBeAg lowers the replication fitness and transcriptionefficiency to levels comparable to that of the wild-type. Our results highlight the role of HBeAg in modulating the early steps in HBV replication. In sum, our findings highlight the role of HBeAg in regulating hepatitis B virus replication fitness and transcription efficiency and new insights on the early steps of replication in the G1896A mutant.
Keywords: G1896A; HBV; HBeAg; HBsAg; Pre-core mutation; Replication fitness; Transcription efficiency; Virion secretion.
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