Identification of bovine papillomavirus E1 mutants with increased transforming and transcriptional activity

J. T. Schiller, E. Kleiner, Elliot Androphy, D. R. Lowry, H. Pfister

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The E1 open reading frame of bovine papillomavirus type 1 (BPV) has been shown previously to encode trans-acting functions, M and R, that are involved in extrachromosomal replication of the viral genome. We have determined that several E1 mutants mapping in both the M and R regions and a single mutant of the upstream regulatory region have a higher transforming activity on mouse C127 cells than the wild-type genome does. A representative mutant in M, a mutant in R, and the upstream regulatory region mutant were complemented in trans by the wild-type genome, but the two E1 mutants did not complement each other, suggesting that they affect the same inhibitory function. A long terminal repeat-activated clone constructed to express the intact E1 open reading frame reversed the high-transformation phenotype of the mutants. In contrast to the high-copy-number autonomous replication of the wild-type genome, the genomes of the E1 mutants were, as previously described for other E1 mutants, integrated at lower copy numbers in the tranformed cells. Relative to the viral genome copy number, both the E1 M and R mutant transformed cells contained an average of 10-fold more BPV-specific transcripts than did the wild-type transformed cells. Cycloheximide treatment of the cells transformed by the E1 mutants did not lead to the rapid 10-fold increase in the accumulation of viral transcripts observed with the wild-type genome. These results suggest either that integration of the BPV genome makes it unresponsive to a labile repressor or that an E1 gene product, containing both M and R sequences, is a repressor of BPV transcription.

Original languageEnglish (US)
Pages (from-to)1775-1782
Number of pages8
JournalJournal of Virology
Volume63
Issue number4
StatePublished - 1989
Externally publishedYes

Fingerprint

Bovine papillomavirus
Bovine papillomavirus 1
Genome
mutants
genome
Nucleic Acid Regulatory Sequences
Viral Genome
Open Reading Frames
Terminal Repeat Sequences
Cycloheximide
DNA Replication
cells
open reading frames
Clone Cells
Phenotype
terminal repeat sequences
cycloheximide
virus replication
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Identification of bovine papillomavirus E1 mutants with increased transforming and transcriptional activity. / Schiller, J. T.; Kleiner, E.; Androphy, Elliot; Lowry, D. R.; Pfister, H.

In: Journal of Virology, Vol. 63, No. 4, 1989, p. 1775-1782.

Research output: Contribution to journalArticle

Schiller, J. T. ; Kleiner, E. ; Androphy, Elliot ; Lowry, D. R. ; Pfister, H. / Identification of bovine papillomavirus E1 mutants with increased transforming and transcriptional activity. In: Journal of Virology. 1989 ; Vol. 63, No. 4. pp. 1775-1782.
@article{c9fbb3a7108940f1b181799f1c649733,
title = "Identification of bovine papillomavirus E1 mutants with increased transforming and transcriptional activity",
abstract = "The E1 open reading frame of bovine papillomavirus type 1 (BPV) has been shown previously to encode trans-acting functions, M and R, that are involved in extrachromosomal replication of the viral genome. We have determined that several E1 mutants mapping in both the M and R regions and a single mutant of the upstream regulatory region have a higher transforming activity on mouse C127 cells than the wild-type genome does. A representative mutant in M, a mutant in R, and the upstream regulatory region mutant were complemented in trans by the wild-type genome, but the two E1 mutants did not complement each other, suggesting that they affect the same inhibitory function. A long terminal repeat-activated clone constructed to express the intact E1 open reading frame reversed the high-transformation phenotype of the mutants. In contrast to the high-copy-number autonomous replication of the wild-type genome, the genomes of the E1 mutants were, as previously described for other E1 mutants, integrated at lower copy numbers in the tranformed cells. Relative to the viral genome copy number, both the E1 M and R mutant transformed cells contained an average of 10-fold more BPV-specific transcripts than did the wild-type transformed cells. Cycloheximide treatment of the cells transformed by the E1 mutants did not lead to the rapid 10-fold increase in the accumulation of viral transcripts observed with the wild-type genome. These results suggest either that integration of the BPV genome makes it unresponsive to a labile repressor or that an E1 gene product, containing both M and R sequences, is a repressor of BPV transcription.",
author = "Schiller, {J. T.} and E. Kleiner and Elliot Androphy and Lowry, {D. R.} and H. Pfister",
year = "1989",
language = "English (US)",
volume = "63",
pages = "1775--1782",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "4",

}

TY - JOUR

T1 - Identification of bovine papillomavirus E1 mutants with increased transforming and transcriptional activity

AU - Schiller, J. T.

AU - Kleiner, E.

AU - Androphy, Elliot

AU - Lowry, D. R.

AU - Pfister, H.

PY - 1989

Y1 - 1989

N2 - The E1 open reading frame of bovine papillomavirus type 1 (BPV) has been shown previously to encode trans-acting functions, M and R, that are involved in extrachromosomal replication of the viral genome. We have determined that several E1 mutants mapping in both the M and R regions and a single mutant of the upstream regulatory region have a higher transforming activity on mouse C127 cells than the wild-type genome does. A representative mutant in M, a mutant in R, and the upstream regulatory region mutant were complemented in trans by the wild-type genome, but the two E1 mutants did not complement each other, suggesting that they affect the same inhibitory function. A long terminal repeat-activated clone constructed to express the intact E1 open reading frame reversed the high-transformation phenotype of the mutants. In contrast to the high-copy-number autonomous replication of the wild-type genome, the genomes of the E1 mutants were, as previously described for other E1 mutants, integrated at lower copy numbers in the tranformed cells. Relative to the viral genome copy number, both the E1 M and R mutant transformed cells contained an average of 10-fold more BPV-specific transcripts than did the wild-type transformed cells. Cycloheximide treatment of the cells transformed by the E1 mutants did not lead to the rapid 10-fold increase in the accumulation of viral transcripts observed with the wild-type genome. These results suggest either that integration of the BPV genome makes it unresponsive to a labile repressor or that an E1 gene product, containing both M and R sequences, is a repressor of BPV transcription.

AB - The E1 open reading frame of bovine papillomavirus type 1 (BPV) has been shown previously to encode trans-acting functions, M and R, that are involved in extrachromosomal replication of the viral genome. We have determined that several E1 mutants mapping in both the M and R regions and a single mutant of the upstream regulatory region have a higher transforming activity on mouse C127 cells than the wild-type genome does. A representative mutant in M, a mutant in R, and the upstream regulatory region mutant were complemented in trans by the wild-type genome, but the two E1 mutants did not complement each other, suggesting that they affect the same inhibitory function. A long terminal repeat-activated clone constructed to express the intact E1 open reading frame reversed the high-transformation phenotype of the mutants. In contrast to the high-copy-number autonomous replication of the wild-type genome, the genomes of the E1 mutants were, as previously described for other E1 mutants, integrated at lower copy numbers in the tranformed cells. Relative to the viral genome copy number, both the E1 M and R mutant transformed cells contained an average of 10-fold more BPV-specific transcripts than did the wild-type transformed cells. Cycloheximide treatment of the cells transformed by the E1 mutants did not lead to the rapid 10-fold increase in the accumulation of viral transcripts observed with the wild-type genome. These results suggest either that integration of the BPV genome makes it unresponsive to a labile repressor or that an E1 gene product, containing both M and R sequences, is a repressor of BPV transcription.

UR - http://www.scopus.com/inward/record.url?scp=0024565085&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024565085&partnerID=8YFLogxK

M3 - Article

C2 - 2538656

AN - SCOPUS:0024565085

VL - 63

SP - 1775

EP - 1782

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 4

ER -