A cis/trans Genetic Test for Pleiotropic Phenotypes Associated with a Frequent Naturally Occurring Mutation at Amino Acid 97 of HBV Core Protein

Hepatitis B virus (HBV) is a major human infectious pathogen. Worldwide, there are more than 350 million chronic carriers of HBV. Sequence divergence within the HBV genome is observed during long-term infection of HBV in patients as a result of the low fidelity of HBV reverse transcriptase. The important roles played by naturally occurring HBV variants have been implicated in the development of chronic hepatitis B. However, functional characterization of HBV variants remains difficult because of the lack of a priori knowledge to predict the possible abnormality of variants and to choose the relevant functional assay accordingly. This issue is further complicated by the possibility that a mutant phenotype could arise from either the trans defect of a mutant protein or the cis defect of a mutated genome.