| Functional analysis of a rare HBV deletion mutant in chronically infected children. | |
| | |
MedLine Citation:
|
PMID: 12646724 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Liver damage caused by chronic hepatitis B virus (HBV) infection may be enhanced through the selection of deleted HBV preS mutants by intracellular accumulation of viral proteins and subsequent cell death. However, the prevalence and impact of such mutants on the clinical course of infection have not yet been studied in children. Serum samples from 60 children (mean age 9.8 y) were investigated by means of PCR and direct sequencing of the entire preS region. Only one patient (1.5%) was found with a mixed HBV population of a deletion spanning 183 nucleotides and wild-type sequences. This mutation alters the HBV large-surface protein and removes the small-surface promoter. To clarify the significance of this mutation, we studied 14 serial serum samples of the child within a follow-up of 10 y. After occurrence of the mutation, the liver enzymes increased, despite seroconversion to anti-HBe. Transfection of an HBV expression construct containing this deletion into human hepatoma cells by using an HBV in vitro replication system showed that the mutant lost the ability of nucleocapsid packaging as a result of alteration of the transmembrane topology of the large surface protein. This effect could not be restored by coexpression of wild-type large- or small-surface proteins in trans. In conclusion, the circulation of HBV preS deletion mutants is rare in childhood. However, our functional and clinical follow-up studies in one child suggest that such a mutant may have the potential to aggravate liver inflammation, especially if corroborated with larger numbers of children. |
| | |
Authors:
|
Patrick Gerner; Heike Marie Clara Schäfer; Reinhild Prange; Dirk Pravitt; Stefan Wirth |
Related Documents
:
|
9696024 - Incidence and clinical consequences of surface and polymerase gene mutations in liver t... 22180724 - Hepatitis c viral kinetics in the era of direct acting antiviral agents and il28b. 7836704 - Analysis of hepatitis b precore region in serum and liver of chronic hepatitis b virus ... 22190394 - Havcr1 gene haplotypes and infection by different viral hepatitis c virus genotypes. 6440364 - Pneumocystis carinii pneumonia treated with alpha-difluoromethylornithine. a prospectiv... 16555284 - Distribution of hepatitis c virus genotypes among hemodialysis patients in tehran--a mu... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2003-03-19 |
Journal Detail:
|
Title: Pediatric research Volume: 53 ISSN: 0031-3998 ISO Abbreviation: Pediatr. Res. Publication Date: 2003 Jun |
Date Detail:
|
Created Date: 2003-06-02 Completed Date: 2004-01-16 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0100714 Medline TA: Pediatr Res Country: United States |
Other Details:
|
Languages: eng Pagination: 891-7 Citation Subset: IM |
Affiliation:
|
Children's Hospital, Helios Klini Kum, Wuppertal, Heusnerstrasse 40, D-42283 Wuppertal, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adolescent Base Sequence Child Child, Preschool DNA Primers Endoplasmic Reticulum / metabolism Female Hepatitis B virus / genetics* Hepatitis B, Chronic / genetics* Humans Infant Male Polymerase Chain Reaction Sequence Deletion |
| Chemical | |
Reg. No./Substance:
|
0/DNA Primers |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A very-short-term intermittency of fetal heart rates and developmental milestone.
Next Document: Changes in 5alpha-pregnane steroids and neurosteroidogenic enzyme expression in the perinatal sheep.