Document Detail

A highly efficient system to produce infectious human papillomavirus: Elucidation of natural virus-host interactions.
MedLine Citation:
PMID:  19342877     Owner:  NLM     Status:  MEDLINE    
A simple, efficient system has been developed to produce high titers of infectious human papillomavirus type 18 (HPV-18) in organotypic raft cultures of primary human keratinocytes (PHKs). Molecular characterization elucidated key early and late events in the reproductive program. The system obviates the need for immortalized cells and allows the analyses of mutant HPV genomes not previously possible. An E6 deletion mutant incapable of causing p53 degradation is defective in viral DNA amplification and capsid protein production. The high levels of p53 protein which accumulated in numerous cells did not lead to apoptosis over a prolonged duration. Time course and metabolic labeling experiments revealed novel interactions with the host. Notably, post-mitotic, differentiated cells are induced by HPV E7 expression to reenter S phase, whereupon host chromosomes replicate, but HPV DNA does not amplify until the cells have progressed to and are arrested in G(2) phase. Here, we present data that strongly suggest that the abundant cytoplasmic viral E1;E4 protein is not responsible for this G(2) arrest, as described in the literature upon ectopic expression in cell lines. We provide additional insights into the viral life cycle and contrast them to conclusions derived from experiments in cell lines.
Louise T Chow; Aaron A Duffy; Hsu-Kun Wang; Thomas R Broker
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-05-19
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  8     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-22     Completed Date:  2009-06-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1319-23     Citation Subset:  IM    
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
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MeSH Terms
DNA, Viral / metabolism
Genetic Techniques*
Host-Pathogen Interactions*
Human papillomavirus 18 / physiology
Papillomaviridae / pathogenicity*,  physiology
Viral Proteins / metabolism
Virion / ultrastructure
Virus Replication
Grant Support
Reg. No./Substance:
0/DNA, Viral; 0/Viral Proteins

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