Defective mutants of hepatitis B virus in the circulation of symptom-free carriers.

A total of 75 clones of hepatitis B virus (HBV) DNA were isolated from the plasma of 4 symptom-free carriers. Each set of clones from a carrier all possessed at least one complete genome, for which the entire nucleotide sequence was determined. A deletion of nucleotide sequence, spanning from 13 to 1071 base pairs, was detected in 17 clones (23%). As many as 16 of them had a deletion in the C gene, with or without the involvement of the P and X genes. The remaining one clone had a deletion restricted to the pre-S region. Accordingly, these defective mutants could not replicate themselves without help from complete HBV co-infecting the same hepatocyte. Defective mutants would have developed during the replication of HBV by reverse transcription of an RNA intermediate, and provide another evidence for a close similarity of HBV with retroviruses.