Treatment of bovine-papillomavirus-type-1 (BPV)-transformed mouse cells with aromatic retinoid and retinoic acid

A novel assay system has been developed in which expression of a human tissue-plasminogen activator (t-PA) gene, carried on a recombinant papillomavirus vector, is used as a marker for the presence of bovine papillomavirus type 1 (BPV-1) within transformed mouse C127 cells. This provides a relatively quick and simple means of identifying and evaluating agents with anti-papillomavirus activity. Using this system the antiviral activity and cytotoxicity of interferon and retinoic acid, have been investigated. After seven subcultures in the presence of 200 Units ml−1 mouse α and β interferon, t-PA expression was completely inhibited, with a concurrent alteration in cellular morphology, and restoration of contact inhibition. In accordance with the problems encountered with interferon therapy of human papillomavirus infections, these effects were dependent on the continued presence of interferon, its removal leading to a rapid return of t-PA expression, and reversion of cells to the transformed phenotype. In comparison, 2.0 μg ml−1 retinoic acid partially reduced t-PA expression (this effect was largely maintained even after removal of the inhibiting compound) but did not affect the transformed cell phenotype. These results are discussed in relation to other in vitro studies and also to the clinical treatment of human papillomavirus (HPV) disease.

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The bovine papillomavirus distal "enhancer" is not cis essential for transformation or for plasmid maintenance

Molecular and Cellular Biology ◽

10.1128/mcb.5.11.3310-3315.1985 ◽

1985 ◽

Vol 5 (11) ◽

pp. 3310-3315

Author(s):

P M Howley ◽

E T Schenborn ◽

E Lund ◽

J C Byrne ◽

J E Dahlberg

Keyword(s):

Cellular Transformation ◽

Transformed Cells ◽

Bovine Papillomavirus ◽

Multicopy Plasmid ◽

Distal Enhancer ◽

Transcriptional Enhancer ◽

Plasmid Maintenance ◽

Viral Genes ◽

Mouse Cells

We constructed a mutant of bovine papillomavirus type 1 (BPV-1) DNA that lacked a transcriptional enhancer located 3' to the polyadenylation site of the early viral RNAs expressed in transformed cells. This mutant DNA, when separated from the procaryotic sequences, transforms mouse cells with an efficiency comparable to that of the full BPV-1 genome, and it exists as a stable multicopy plasmid in transformed cells. The BPV-1 distal enhancer suppresses the effects of a cis-inhibitory element in pML2 sequences but is not essential for the expression of the viral genes involved in cellular transformation or plasmid maintenance.

Download Full-text

The bovine papillomavirus distal "enhancer" is not cis essential for transformation or for plasmid maintenance.

Molecular and Cellular Biology ◽

10.1128/mcb.5.11.3310 ◽

1985 ◽

Vol 5 (11) ◽

pp. 3310-3315 ◽

Cited By ~ 13

Author(s):

P M Howley ◽

E T Schenborn ◽

E Lund ◽

J C Byrne ◽

J E Dahlberg

Keyword(s):

Cellular Transformation ◽

Transformed Cells ◽

Bovine Papillomavirus ◽

Multicopy Plasmid ◽

Distal Enhancer ◽

Transcriptional Enhancer ◽

Plasmid Maintenance ◽

Viral Genes ◽

Mouse Cells

We constructed a mutant of bovine papillomavirus type 1 (BPV-1) DNA that lacked a transcriptional enhancer located 3' to the polyadenylation site of the early viral RNAs expressed in transformed cells. This mutant DNA, when separated from the procaryotic sequences, transforms mouse cells with an efficiency comparable to that of the full BPV-1 genome, and it exists as a stable multicopy plasmid in transformed cells. The BPV-1 distal enhancer suppresses the effects of a cis-inhibitory element in pML2 sequences but is not essential for the expression of the viral genes involved in cellular transformation or plasmid maintenance.

Download Full-text