Persistence of hepatitis B viral DNA after serological recovery from hepatitis B virus infection.
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.
Blum
H E
HE
Massachusetts General Hospital, Harvard Medical School, Charlestown 02129.
Liang
T J
TJ
Galun
E
E
Wands
J R
JR
D000368:Aged; D000936:Antigen-Antibody Complex; D001483:Base Sequence; D003062:Codon; D004261:DNA Replication; D004279:DNA, Viral / Q000378:metabolism*; D005814:Genes, Viral; D006509:Hepatitis B / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D014158:Transcription, Genetic
D000936:Antigen-Antibody Complex; D003062:Codon; D004279:DNA, Viral; D006513:Hepatitis B e Antigens