Large T-Antigen and Sequences within the Regulatory Region of JC Virus Both Contribute to the Features of JC Virus DNA Replication

Virology ◽  
1993 ◽  
Vol 197 (2) ◽  
pp. 537-548 ◽  
Author(s):  
Elisabeth Sock ◽  
Michael Wegner ◽  
Elizabeth A. Fortunato ◽  
Friedrich Grummt
Keyword(s):  
Dna Replication ◽  
Jc Virus ◽  
Regulatory Region ◽  
T Antigen ◽  
Large T Antigen

scholarly journals Species-Specific Elements in the Large T-Antigen J Domain Are Required for Cellular Transformation and DNA Replication by Simian Virus 40

2000 ◽  
Vol 20 (15) ◽  
pp. 5749-5757 ◽  
Author(s):  
Christopher S. Sullivan ◽  
James D. Tremblay ◽  
Sheara W. Fewell ◽  
John A. Lewis ◽  
Jeffrey L. Brodsky ◽  
...  
Keyword(s):  
Dna Replication ◽  
Jc Virus ◽  
Simian Virus 40 ◽  
Cellular Transformation ◽  
Simian Virus ◽  
T Antigen ◽  
Large T Antigen ◽  
Sv40 Large T Antigen ◽  
J Domain ◽  
Species Specific

ABSTRACT The J domain of simian virus 40 (SV40) large T antigen is required for efficient DNA replication and transformation. Despite previous reports demonstrating the promiscuity of J domains in heterologous systems, results presented here show the requirement for specific J-domain sequences in SV40 large-T-antigen-mediated activities. In particular, chimeric-T-antigen constructs in which the SV40 T-antigen J domain was replaced with that from the yeast Ydj1p or Escherichia coli DnaJ proteins failed to replicate in BSC40 cells and did not transform REF52 cells. However, T antigen containing the JC virus J domain was functional in these assays, although it was less efficient than the wild type. The inability of some large-T-antigen chimeras to promote DNA replication and elicit cellular transformation was not due to a failure to interact with hsc70, since a nonfunctional chimera, containing the DnaJ J domain, bound hsc70. However, this nonfunctional chimeric T antigen was reduced in its ability to stimulate hsc70 ATPase activity and unable to liberate E2F from p130, indicating that transcriptional activation of factors required for cell growth and DNA replication may be compromised. Our data suggest that the T-antigen J domain harbors species-specific elements required for viral activities in vivo.

scholarly journals Kilham Polyomavirus: Activation of Gene Expression and DNA Replication in Mouse Fibroblast Cells by an Enhancer Substitution

2001 ◽  
Vol 75 (21) ◽  
pp. 10015-10023 ◽  
Author(s):  
Shouting Zhang ◽  
Göran Magnusson
Keyword(s):  
Gene Expression ◽  
Dna Replication ◽  
T Antigen ◽  
Mouse Fibroblast ◽  
Fibroblast Cells ◽  
Large T Antigen ◽  
Wild Type ◽  
3T3 Cells ◽  
Late Promoter ◽  
Substitution Mutant

ABSTRACT The Kilham strain of polyomavirus (KV) infects vascular endothelial cells in vivo (J. E. Greenlee, Infect. Immun. 26:705–713, 1979), but no permissive cell type for growth of the virus in vitro has been identified. The failure of KV DNA to replicate in mouse fibroblast cells after transfection suggested that viral gene expression had narrow cell specificity. A KV substitution mutant having a part of the regulatory region of KV DNA replaced with a segment of the polyomavirus transcriptional enhancer was constructed. The substitution mutant was able to replicate in transfected 3T3 cells, and the newly replicated viral DNA associated with protein to form particles with the density of virions in CsCl equilibrium gradients. However, these particles were noninfectious when tested on 3T3 cells, suggesting that absorption or uptake of virus particles was defective for these cells. Analysis of early and late promoter activities by luciferase reporter gene expression showed that the enhancer substitution had a moderate positive effect on early gene expression and a large effect on the expression of the late genes. KV large T antigen inhibited the activities of both the wild-type and the substitution mutant early promoter, whereas only the mutant late promoter was activated under the same conditions. A comparison of the KV and polyomavirus large T antigens showed that they were not interchangeable in the initiation of KV and polyomavirus DNA synthesis. Furthermore, the wild-type KV origin of DNA replication was less active than the mutant structure in the presence of saturating amounts of KV large T antigen. Together, our data demonstrate several differences between the two types of large T antigen in their interactions with cellular proteins.

scholarly journals Structures of large T antigen at the origin of SV40 DNA replication by atomic force microscopy

1994 ◽  
Vol 66 (2) ◽  
pp. 293-298 ◽  
Author(s):  
I.A. Mastrangelo ◽  
M. Bezanilla ◽  
P.K. Hansma ◽  
P.V. Hough ◽  
H.G. Hansma
Keyword(s):  
Atomic Force Microscopy ◽  
Dna Replication ◽  
T Antigen ◽  
Large T Antigen ◽  
Force Microscopy ◽  
Atomic Force ◽  
Sv40 Dna

Polyomavirus-plasmid recombinants capable of replicating have an enhanced transforming potential

1983 ◽  
Vol 3 (9) ◽  
pp. 1670-1674
Author(s):  
W J Muller ◽  
M A Naujokas ◽  
J A Hassell
Keyword(s):  
Dna Replication ◽  
Mammalian Cells ◽  
T Antigen ◽  
Viral Gene ◽  
Large T Antigen ◽  
Viral Dna ◽  
Viral Dna Replication ◽  
Transfected Cells ◽  
Cis Acting ◽  
Viral Gene Product

The frequency of transformation of rodent fibroblasts by polyomavirus is enhanced by a viral gene product, large T-antigen. However, this effect of large T-antigen cannot be demonstrated with pBR322-cloned viral DNA. Recently, it was discovered that pBR322 contains cis-acting sequences inhibitory to DNA replication in mammalian cells. Because polyomavirus large T-antigen is required for viral DNA replication, we examined the possibility that our inability to demonstrate a requirement for large T-antigen in transformation with pBR322-cloned viral DNA was due to the failure of the chimeric DNA to replicate in the transfected cells. To this end we constructed polyomavirus recombinant molecules with a plasmid (pML-2) that lacks these "poison" sequences and measured their capacity to transform cells. Here we report that recombinant plasmids capable of replicating in the transfected cells transform these cells at frequencies approximately sixfold greater than their replication-defective counterparts.

scholarly journals Biochemical Characterization and Localization of JC Virus Large T Antigen Phosphorylation Domains

Virology ◽  
1995 ◽  
Vol 212 (2) ◽  
pp. 295-308 ◽  
Author(s):  
Jennifer J. Swenson ◽  
Richard J. Frisque
Keyword(s):  
Biochemical Characterization ◽  
Jc Virus ◽  
T Antigen ◽  
Large T Antigen

scholarly journals High-Throughput Cell-Based Screen for Chemicals That Inhibit Infection by Simian Virus 40 and Human Polyomaviruses

2009 ◽  
Vol 83 (11) ◽  
pp. 5630-5639 ◽  
Author(s):  
Edward C. Goodwin ◽  
Walter J. Atwood ◽  
Daniel DiMaio
Keyword(s):  
High Throughput ◽  
Ellagic Acid ◽  
Viral Vector ◽  
Jc Virus ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Early Gene ◽  
Large T Antigen ◽  
Human Polyomaviruses

ABSTRACT We developed a high-throughput, cell-based screen to identify chemicals that inhibit infection by the primate polyomaviruses. The screen is based on the detection of compounds that inhibit the ability of a replication-defective simian virus 40 (SV40)-based viral vector to cause growth arrest in HeLa cells by repressing the expression of the endogenous human papillomavirus E7 oncogene in these cells. We identified two compounds, ellagic acid and spiperone, that suppressed the ability of the SV40 recombinant virus to inhibit cellular DNA synthesis. These compounds caused a marked reduction of the ability of wild-type SV40 to productively infect permissive monkey cells, even when the compounds were added several hours after infection. The fraction of cells expressing SV40 large T antigen and the levels of T antigen mRNA were reduced in infected human and monkey cells treated with ellagic acid and spiperone, suggesting that these compounds block a step in the virus life cycle prior to SV40 early gene expression. Ellagic acid and spiperone also inhibited large T antigen expression by BK virus and JC virus, two important, pathogenic human polyomaviruses.

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