Characterization and biological properties of a hepatitis B virus isolated from a patient without hepatitis B virus serologic markers.
We have developed a rapid method to characterize genomic diversity of low-level hepatitis B and related viral agents after their identification in serum by high-affinity HBsAg-antibody monoclonal antibody capture and subsequent polymerase chain reaction amplification. Serum from an individual with chronic liver disease and without hepatitis B virus serological markers but reactive by monoclonal antibody capture/polymerase chain reaction amplification was inoculated into a chimpanzee. After inoculation, an acute hepatitis B virus-like hepatitis developed in the chimpanzee. Analysis of serial liver biopsy samples showed the persistence of hepatitis B virus DNA for more than 17 mo after resolution of acute hepatitis and seroconversion. Applying the technique of restriction enzyme fragment analysis to serial chimpanzee liver biopsy samples and acute-phase sera, along with the serum inoculum, we established that all hepatitis B virus DNA sequences are derived from the same viral agent. We present evidence that the viral DNA persisted as a nonreplicating episomal form in the nucleus of hepatocytes. This study demonstrates that after clinical and serological recovery from an acute hepatitis, there may be persistence of low-level hepatitis B virus-related genome in the liver despite the presence of antibodies to HBsAg. Such persistence of viral genome may be a natural sequela of infection and may serve as a source of viral latency and possible reactivation. Finally, cloning and complete nucleic-acid sequencing of this virus have demonstrated multiple nucleotide and amino acid changes compared with all known hepatitis B virus subtypes. These changes may have contributed in part to a different antigenic composition or immunological reactivity of the host to this hepatitis B virus isolate.
Liang
T J
TJ
Department of Medicine, Harvard Medical School, Massachusetts General Hospital Cancer Center, Charlestown 02129.
Blum
H E
HE
Wands
J R
JR
D000818:Animals; D000911:Antibodies, Monoclonal; D000937:Antigen-Antibody Reactions; D001483:Base Sequence; D004262:DNA Restriction Enzymes / Q000032:analysis; D004279:DNA, Viral; D005814:Genes, Viral; D006509:Hepatitis B / Q000276:immunology / Q000382:microbiology*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D016133:Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D004262:DNA Restriction Enzymes