Replication-defective missense mutations within the terminal protein and spacer/intron regions of the polymerase gene of human hepatitis B virus

We have analyzed 11 independent mutations located at various domains of the polymerase gene (pol) of human hepatitis B virus. Surprisingly, one of the two missense mutants within the spacer/intron region appears to be lethal. This result further defines the N-terminal limit of the reverse transcriptase domain. Alternatively, it suggests the potential existence of a novel domain with an unknown function. Two missense mutations within the terminal protein (TP) domain appear to be replication-defective as well, suggesting a functionally essential role of the TP domain in DNA replication.