Document Detail


Hepatitis B virus enhances transduction of human hepatocytes by SV40-based vectors.
MedLine Citation:
PMID:  15123369     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: Chronic HBV infection, a world-wide epidemic, can lead to chronic hepatitis and eventually to cirrhosis and hepatocellular carcinoma. The liver poses obstacles for many available gene-transfer vectors. SV40-based vectors can transduce human hepatic and hematopoietic cells. We studied the effect of HBV on the transduction - efficiency of human hepatic cells by SV40 - based vectors. METHODS: A SV40-vector carrying the luciferase gene, and wild-type SV40, were used to assess transduction efficiency of human HBV-positive and HBV-negative hepatic cells. Transduction efficiency was measured as luciferase activity or by T-antigen staining. To evaluate whether differences in transduction efficiency are due to cell recognition and/or nuclear transport, MHC-I receptors were measured by FACS analysis and SV40-DNA was extracted from the nuclei of transduced cells and quantified. RESULTS: Two HBV-positive cell-lines, HepG2.2.2.15 and FLC4-A10II, were transduced significantly more efficiently than their parental HBV-negative cell-lines. Transient transfection of HuH-7 cells with the HBV genome also increased transduction efficiency. The level of MHC-I, the cellular receptor for SV40, was comparable in all the cell-lines studied. However, soon after infection with SV40, the nuclei of HepG2.2.2.15 contained >6-fold more SV40-DNA than HepG2. CONCLUSIONS: HBV increases transduction by SV40-vectors. This is due to enhanced vector entry and/or transport into the nucleus. SV40-vectors appear to have a potential for gene therapy for the treatment of HBV infections.
Authors:
Uri Arad; Jonathan Axelrod; Orly Ben-nun-Shaul; Ariella Oppenheim; Eithan Galun
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hepatology     Volume:  40     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-05-04     Completed Date:  2004-11-10     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  520-6     Citation Subset:  IM    
Affiliation:
Department of Hematology and Goldyne Savad Gene Therapy Institute, The Hebrew University-Hadassah Medical School and Hadassah University Hospital, Jerusalem, Israel.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Cell Nucleus / metabolism
DNA, Viral / metabolism
Dimerization
Gene Expression
Genetic Vectors*
Genome, Viral
Hepatitis B virus / metabolism,  physiology*
Hepatocytes / physiology*
Histocompatibility Antigens Class I / metabolism
Humans
Polyomavirus Infections / metabolism
Promoter Regions, Genetic
Receptors, Virus / metabolism
Simian virus 40 / genetics*
Transduction, Genetic*
Transfection
Tumor Virus Infections / metabolism
Viral Proteins / metabolism
Chemical
Reg. No./Substance:
0/DNA, Viral; 0/Histocompatibility Antigens Class I; 0/Receptors, Virus; 0/Viral Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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