Latent hepatitis B virus infection in healthy individuals with antibodies to hepatitis B core antigen.
Several recent reports have shown that hepatitis B virus (HBV) could be frequently transmitted to the recipients from donors who have antibodies to hepatitis B core antigen (anti-HBc) through liver transplantation. We provide here the molecular evidence of latent HBV infection accompanied with ongoing viral replication in the liver tissue of anti-HBc-positive healthy individuals. HBV DNA was detectable in 13 of 14 healthy donors who were positive for both anti-HBc and antibodies to hepatitis B surface antigen (anti-HBs), but in none of 3 who were positive for anti-HBs alone. The detected HBV genomes from these subjects included covalently closed circular DNA and pregenomic RNA, the replication intermediate of HBV. Notably, 5 of 7 cases tested were predominantly infected with wild type HBV strains without any mutations in the precore and core promoter regions under the presence of circulating antibody to hepatitis B e antigen. Interestingly, a predominant clone detected in one donor showed a 63-nucleotide deletion in the precore region including an encapsidation signal sequence. Our findings indicate that the majority of healthy individuals positive for anti-HBc, which had been assumed to denote a past history of transient HBV infection, were latently infected with the episomal form of HBV accompanied by ongoing viral replication and few nucleotide mutations in the precore and core regions.
Marusawa
H
H
Division of Gastroenterology, Department of Medicine, The Institute for Virus Research, Kyoto University, Kyoto, Japan.
Uemoto
S
S
Hijikata
M
M
Ueda
Y
Y
Tanaka
K
K
Shimotohno
K
K
Chiba
T
T
D000328:Adult; D000368:Aged; D001483:Base Sequence / Q000235:genetics; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D016679:Genome, Viral; D006509:Hepatitis B / Q000276:immunology* / Q000821:virology*; D006510:Hepatitis B Antibodies / Q000032:analysis*; D006511:Hepatitis B Antigens / Q000032:analysis; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D017735:Virus Latency
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006511:Hepatitis B Antigens; D006512:Hepatitis B Core Antigens