Document Detail

Deleterious effects of hepatitis delta virus replication on host cell proliferation.
MedLine Citation:
PMID:  11264349     Owner:  NLM     Status:  MEDLINE    
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.
D Wang; J Pearlberg; Y T Liu; D Ganem
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of virology     Volume:  75     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-03-26     Completed Date:  2001-04-12     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3600-4     Citation Subset:  IM    
Departments of Microbiology and Medicine and Howard Hughes Medical Institute, University of California Medical Center, San Francisco, California 94143, USA.
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MeSH Terms
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*
RNA, Messenger / analysis,  genetics
RNA, Viral / biosynthesis,  genetics
Time Factors
Tumor Necrosis Factor-alpha / pharmacology
Viral Proteins / biosynthesis
Virus Replication* / drug effects
Reg. No./Substance:
0/RNA, Messenger; 0/RNA, Viral; 0/Tumor Necrosis Factor-alpha; 0/Viral Proteins; 50-76-0/Dactinomycin

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