Integration of hepatitis B virus DNA into chromosomal DNA during acute hepatitis B.
OBJECTIVE
To examine the serum from black African patients with acute hepatitis B to ascertain if integrants of viral DNA can be detected in fragments of cellular DNA leaking from damaged hepatocytes into the circulation.


METHODS
DNA was extracted from the sera of five patients with uncomplicated acute hepatitis B and one with fulminant disease. Two subgenomic PCRs designed to amplify the complete genome of HBV were used and the resulting amplicons were cloned and sequenced.


RESULTS
HBV and chromosomal DNA were amplified from the sera of all the patients. In one patient with uncomplicated disease, HBV DNA was integrated into host chromosome 7 q11.23 in the WBSCR1 gene. The viral DNA comprised 200 nucleotides covering the S and X genes in opposite orientation, with a 1 169 nucleotide deletion. The right virus/host junction was situated at nucleotide 1,774 in the cohesive overlap region of the viral genome, at a preferred topoisomerase I cleavage motif. The chromosomal DNA was not rearranged. The patient made a full recovery and seroconverted to anti-HBs- and anti-HBe-positivity. Neither HBV nor chromosomal DNA could be amplified from his serum at that time.


CONCLUSIONS
Integration of viral DNA into chromosomal DNA may occur rarely during acute hepatitis B and, with clonal propagation of the integrant, might play a role in hepatocarcinogenesis.
Kimbi
Gerald C
GC
Department of Medicine, University of the Witwatersrand Medical School, 7 York Road, Parktown 2193, Johannesburg, South Africa.
Kramvis
Anna
A
Kew
Michael C
MC
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002897:Chromosomes, Human, Pair 7 / Q000821:virology*; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D005260:Female; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D016662:Virus Integration
D004279:DNA, Viral