Integration of Hepatitis B Virus DNA into Chromosomal DNA During Acute Hepatitis B
Overview
Authors
Affiliations
Aim: 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.
Conclusion: 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.
The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy.
Zhang M, Chen H, Liu H, Tang H Biomark Res. 2024; 12(1):84.
PMID: 39148134 PMC: 11328401. DOI: 10.1186/s40364-024-00611-y.
Salpini R, DAnna S, Benedetti L, Piermatteo L, Gill U, Svicher V Front Microbiol. 2022; 13:972687.
PMID: 36118192 PMC: 9478028. DOI: 10.3389/fmicb.2022.972687.
van Buuren N, Ramirez R, Soulette C, Suri V, Han D, May L JHEP Rep. 2022; 4(4):100449.
PMID: 35295767 PMC: 8918852. DOI: 10.1016/j.jhepr.2022.100449.
Li Y, Wu H, Liu C Int J Mol Sci. 2021; 22(17).
PMID: 34502289 PMC: 8431721. DOI: 10.3390/ijms22179380.
Zhang D, Zhang K, Protzer U, Zeng C J Clin Transl Hepatol. 2021; 9(3):399-408.
PMID: 34221926 PMC: 8237140. DOI: 10.14218/JCTH.2021.00062.