Selection of a precore mutant of hepatitis B virus and reactivation of chronic hepatitis B acquired in childhood

Bortolotti, Flavia; Crivellaro, Carlo; Brunetto, Maurizia Rossana; Cardrobbi, P.; Bertolini, A.; Alberti, Alfredo

doi:10.1016/s0022-3476(05)80956-4

Cited by 14 publications

(7 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…been sought in the preCore/core ORF. Several studies have found the emergence of preCore stop codon mutants, particularly at nt 1896 A after the time of reactivation [Raimondo et al, 1990;Bortolotti et al, 1993]. However, many more cases are reported where preC stop mutants were observed even before reactivation or where reactivation was not accompanied by HBeAgdefective variants [Takeda et al, 1990;Loriot et al, 1995].…”

Section: Table I Nucleotide Exchanges From Patient 1 Inmentioning

confidence: 99%

Hepatitis B virus core promoter mutations in children with multiple anti-HBe/HBeAg reactivations result in enhanced promoter activity

Gerner¹,

Lausch²,

Friedt

et al. 1999

J. Med. Virol.

View full text Add to dashboard Cite

Sera of two children were examined to determine whether specific hepatitis B virus (HBV) mutants may contribute to anti-hepatitis B e/hepatitis B e antigen (anti-HBe/HBeAg) reactivations during the course of chronic hepatitis B. The full-length HBV genome isolated from sera of patient 1 and the basic core promoter (BCP) from patient 2 were amplified and sequenced before and after several reactivations. The functional significance of the mutant BCP from patient 1 was studied using the luciferase assay. In both patients, rare mutations were found in the BCP at nucleotides 1764(G-->T)/1766(C-->G) and 1766(C-->T)/1768(T-->A) in case 1 and 2, respectively. In the BCP from patient 1, a putative new binding site for the transcription factor hepatocyte nuclear factor 3 (HNF3) was generated. The functional analyses of the mutant showed a 2.8-fold increase of core promoter activity, whereas the BCP variant of patient 2 was also identified to result in enhanced promoter activity. The alignment of full-length genomes from child 1 to the reference sequence showed 61 nucleotide substitutions. Furthermore, the time of reactivations from child 1 was always accompanied by selection of a precore mutation at nucleotide position 1899. In liver tissue of patient 1 before development of hepatocellular carcinoma only free viral sequences were found, whereas a single site integration of HBV was detected in hepatocytes after activation of carcinogenesis. Specific mutations in the HBV BCP of the two patients that are rarely present in chronic carriers were identified to increase the core promoter activity possibly by altering transcription factor binding, suggesting that these variants may be involved in the pathogenesis of frequent HBV reactivations.

show abstract

Section: Table I Nucleotide Exchanges From Patient 1 Inmentioning

confidence: 99%

Hepatitis B virus core promoter mutations in children with multiple anti-HBe/HBeAg reactivations result in enhanced promoter activity

Gerner¹,

Lausch²,

Friedt

et al. 1999

J. Med. Virol.

View full text Add to dashboard Cite

show abstract

“…This mutation results in a stop codon for the precore open reading frame (4) and was suggested to induce HBeAg loss and promote HBeAg seroconversion (5,6). However, this mutation does not exist in every case of HBeAg seroconversion (7,8).…”

mentioning

confidence: 98%

Longitudinal Study on Mutation Profiles of Core Promoter and Precore Regions of the Hepatitis B Virus Genome in Children

Chang

Tsuei

2004

Pediatr Res

View full text Add to dashboard Cite

“…1 For example, precore G to A stop codon mutant at nucleotide position 1896 is detected in fulminant hepatitis, acute hepatitis, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). [2][3][4][5][6][7][8] We have addressed the temporal changes in this mutation in chronic HBV infection in children. 9 Because hepatitis B core antigen (HBcAg) is the target for the cytotoxic T lymphocyte (CTL) mediated lysis of HBV infected hepatocytes, [10][11][12] it is also susceptible to mutation.…”

mentioning

confidence: 99%

Different hepatitis B virus core gene mutations in children with chronic infection and hepatocellular carcinoma

Chang²,

Hsu³

et al. 2003

Gut

View full text Add to dashboard Cite

Background: The significance of mutations of hepatitis B virus (HBV) precore/core antigen in causing persistent infection and subsequent liver diseases is debatable. Aim: To investigate HBV core gene sequence changes in children with chronic HBV infection and their implications in hepatocellular carcinoma (HCC). Methods: Thirty one chronic HBV infected children with documented hepatitis B e antigen seroconversion selected from 415 long term carrier children and 12 HBV related HCC children were studied. Four serial serum samples before and after hepatitis B e antigen seroconversion from each of the 31 children, and one serum sample taken from the 12 HCC children were subjected to HBV core gene sequence analysis. Results: Mutations accumulated as chronic infection persisted and most frequently occurred at core gene codon 21 (29%), codon 147 (29%), codon 65 (16%), and precore stop codon 28 (74%) in the 31 chronic HBV infected children. Core gene mutation sites in HCC children were identified at core codons 74, 87, and 159. HCC children had more mutations in the core gene than those with chronic HBV infection (p=0.013). Conclusion: Accumulation of mutations of HBV core region in HCC children differ from those in chronic HBV infected children. This may be a clue to the pathogenesis of paediatric HCC.

show abstract

Selection of a precore mutant of hepatitis B virus and reactivation of chronic hepatitis B acquired in childhood

Cited by 14 publications

References 7 publications

Hepatitis B virus core promoter mutations in children with multiple anti-HBe/HBeAg reactivations result in enhanced promoter activity

Hepatitis B virus core promoter mutations in children with multiple anti-HBe/HBeAg reactivations result in enhanced promoter activity

Longitudinal Study on Mutation Profiles of Core Promoter and Precore Regions of the Hepatitis B Virus Genome in Children

Different hepatitis B virus core gene mutations in children with chronic infection and hepatocellular carcinoma

Contact Info

Product

Resources

About