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. 1991 Apr;65(4):1836–1842. doi: 10.1128/jvi.65.4.1836-1842.1991

Naturally occurring missense mutation in the polymerase gene terminating hepatitis B virus replication.

H E Blum 1, E Galun 1, T J Liang 1, F von Weizsäcker 1, J R Wands 1
PMCID: PMC239993  PMID: 2002544

Abstract

A hepatitis B virus (HBV) genome was cloned from human liver. Numerous mutations in all viral genes define this HBV DNA as a mutant, divergent from all known HBV DNA sequences. Functional analyses of this mutant demonstrated a defect blocking viral DNA synthesis. The genetic basis of this defect was identified as a single missense mutation in the 5' region of the viral polymerase gene, resulting in the inability to package pregenomic RNA into core particles. The replication defect could be trans-complemented by a full-length wild-type, but not by a full-length mutant or 3'-truncated wild-type, polymerase gene construct. Our findings indicate a critical role of the 5' polymerase gene region in the life cycle of the virus and suggest that introducing missense mutations in this region can be a strategy to terminate viral replication in vivo.

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