| Deleterious effects of hepatitis delta virus replication on host cell proliferation. | |
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MedLine Citation:
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PMID: 11264349 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hepatitis delta virus (HDV) infection and spread in vivo are dependent upon coinfection by hepatitis B virus (HBV), and dual HDV/HBV infection is frequently more severe than HBV infection alone, raising the possibility that HDV infection may be deleterious to cells. Here we have examined the effects of HDV replication on the long-term growth of cultured cells. Our results show that most cells transfected with HDV cDNA do not give rise to stable cell lines expressing viral antigens or replicative intermediates; in addition, cotransfection of HDV replicons with a plasmid vector expressing a hygromycin resistance marker results in a dose-dependent impairment of hygromycin-resistant colony formation. When cells transfected with replication-competent HDV cDNA are followed prospectively, a progressive decline in viral RNA replication and a steady decrease in the proportion of cells expressing delta antigen are observed. However, in transient transfection assays, no evidence was found to link HDV replication to apoptosis or to cell cycle arrest, nor did HDV replication confer on host cells enhanced sensitivity to inducers of apoptosis. Thus, HDV replication does not appear to be acutely cytotoxic. However, in dividing cells HDV replication is associated with a subtler growth disadvantage, leading to selection in culture for cells displaying diminished HDV expression. This effect would not be expected to cause hepatitis in vivo but might contribute to impaired liver regeneration in the setting of ongoing hepatocellular injury. |
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Authors:
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D Wang; J Pearlberg; Y T Liu; D Ganem |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of virology Volume: 75 ISSN: 0022-538X ISO Abbreviation: J. Virol. Publication Date: 2001 Apr |
Date Detail:
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Created Date: 2001-03-26 Completed Date: 2001-04-12 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 3600-4 Citation Subset: IM |
Affiliation:
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Departments of Microbiology and Medicine and Howard Hughes Medical Institute, University of California Medical Center, San Francisco, California 94143, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle / drug effects Cell Division* / drug effects Cell Line Dactinomycin / pharmacology Flow Cytometry Gene Expression / drug effects Hela Cells Hepatitis Delta Virus / drug effects, pathogenicity*, physiology* Humans RNA, Messenger / analysis, genetics RNA, Viral / biosynthesis, genetics Time Factors Transfection Tumor Necrosis Factor-alpha / pharmacology Viral Proteins / biosynthesis Virus Replication* / drug effects |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/RNA, Viral; 0/Tumor Necrosis Factor-alpha; 0/Viral Proteins; 50-76-0/Dactinomycin |
| Comments/Corrections | |
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