Persistence of hepatitis B viral DNA after serological recovery from hepatitis B virus infection

Hepatology. 1991 Jul;14(1):56-63. doi: 10.1002/hep.1840140110.


Chronic hepatitis B virus infection is a major medical problem worldwide. Apart from HBsAg carriers, hepatitis B virus has also been identified in some HBsAg-individuals with or without antibodies to viral antigens. The molecular mechanisms underlying hepatitis B virus persistence in HBsAg-individuals are unresolved, however. To identify a possible genetic basis for viral persistence, we cloned the viral genome from the liver of a patient serologically immune to hepatitis B virus infection. DNA sequence analysis of the complete viral genome identified numerous mutations in all viral genes. Analysis of the biological effects of these mutations revealed three major findings: a low level of HBsAg synthesis, absence of HBeAg production and a defect terminating viral replication. These data suggest that mutations accumulating during the natural course of hepatitis B virus infection may be a mechanism underlying viral persistence in HBsAg-individuals, presumably through escape from immune surveillance.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Antigen-Antibody Complex*
  • Base Sequence
  • Codon
  • DNA Replication
  • DNA, Viral / metabolism*
  • Genes, Viral
  • Hepatitis B / immunology*
  • Hepatitis B e Antigens / biosynthesis
  • Hepatitis B virus / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Transcription, Genetic


  • Antigen-Antibody Complex
  • Codon
  • DNA, Viral
  • Hepatitis B e Antigens