scholarly journals Simian virus 40 (SV40)-transgenic mice that develop tumors are specifically tolerant to SV40 T antigen.

1987 ◽  
Vol 165 (2) ◽  
pp. 417-427 ◽  
Author(s):  
S J Faas ◽  
S Pan ◽  
C A Pinkert ◽  
R L Brinster ◽  
B B Knowles
Keyword(s):  
Immune Tolerance ◽  
Transgenic Line ◽  
Simian Virus 40 ◽  
Humoral Response ◽  
Simian Virus ◽  
T Antigen ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Sv40 T Antigen ◽  
Transgenic Lines

The ability to mount an immune response to simian virus 40 (SV40) T antigen was evaluated using mice from two distinct SV40 transgenic lines derived from injection of the same gene construct. Our studies demonstrate functional immune tolerance to SV40 T antigen in a SV40 transgenic line that consistently develops tumors of the choroid plexus by 7 mo of age. Antibodies to SV40 T antigen are undetectable in the serum of these animals; furthermore, mice from this line are unable to generate SV40-specific CTL after primary or secondary immunization with the virus, although they mount a normal CTL response to vaccinia virus when appropriately immunized. In contrast, we find that mice from a second transgenic line of low tumor incidence can mount a humoral response to SV40 T antigen, and upon immunization they generally respond with a vigorous cytotoxic T cell response to SV40 T antigen. These data suggest that specific immune tolerance to the product of an integrated viral oncogene may be induced, and is likely a reflection of the time in development at which the gene product first appears. Immune tolerance or responsiveness to the endogenous oncogene product may in turn play a role in the tumorigenic potential of such genes.

Replication of cloned DNA containing the Alu family sequence during cell extract-promoting simian virus 40 DNA synthesis

1984 ◽  
Vol 4 (8) ◽  
pp. 1476-1482
Author(s):  
H Ariga
Keyword(s):  
Dna Replication ◽  
Dna Synthesis ◽  
Rna Polymerase Iii ◽  
Simian Virus 40 ◽  
Cell Extract ◽  
Simian Virus ◽  
T Antigen ◽  
Sv40 T Antigen ◽  
Sv40 Dna

The replicating activity of several cloned DNAs containing putative origin sequences was examined in a cell-free extract that absolutely depends on simian virus 40 (SV40) T antigen promoting initiation of SV40 DNA replication in vitro. Of the three DNAs containing the human Alu family sequence (BLUR8), the origin of (Saccharomyces cerevisiae plasmid 2 micron DNA (pJD29), and the yeast autonomous replicating sequence (YRp7), only BLUR8 was active as a template. Replication in a reaction mixture with BLUR8 as a template was semiconservative and not primed by a putative RNA polymerase III transcript synthesized on the Alu family sequence in vitro. Pulse-chase experiments showed that the small-sized DNA produced in a short-term incubation was converted to full-length closed circular and open circular DNAs in alkaline sucrose gradients. DNA synthesis in extracts began in a region of the Alu family sequence and was inhibited 80% by the addition of anti-T serum. Furthermore, partially purified T antigen bound the Alu family sequence in BLUR8 by the DNA-binding immunoassay. These results suggest that SV40 T antigen recognizes the Alu family sequence, similar to the origin sequence of SV40 DNA, and initiates semiconservative DNA replication in vitro.

Antibody response to human papovavirus JC (JCV) and simian virus 40 (SV40) T antigens in SV40 T antigen-transgenic mice

Virology ◽  
1992 ◽  
Vol 190 (1) ◽  
pp. 459-464 ◽  
Author(s):  
Satvir S. Tevethia ◽  
Melanie Epler ◽  
Ingo Georgoff ◽  
Angie Teresky ◽  
Marty Marlow ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Antibody Response ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Sv40 T Antigen ◽  
T Antigens ◽  
Human Papovavirus

The growth-stimulatory effect of simian virus 40 T antigen requires the interaction of insulinlike growth factor 1 with its receptor

1992 ◽  
Vol 12 (11) ◽  
pp. 5069-5077
Author(s):  
P Porcu ◽  
A Ferber ◽  
Z Pietrzkowski ◽  
C T Roberts ◽  
M Adamo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Serum Free Medium ◽  
Free Medium ◽  
3T3 Cells ◽  
Sv40 T Antigen ◽  
Serum Free ◽  
Insulinlike Growth Factor

We have used a plasmid expressing a temperature-sensitive (ts) mutant of simian virus 40 (SV40) T antigen, stably transfected into 3T3 cells, to study the role of insulinlike growth factor 1 (IGF-1) and its receptor in T-antigen-mediated growth. While 3T3 cells do not grow in serum-free medium, in 1% serum, or with the sole addition of either platelet-derived growth factor (PDGF) or IGF-1, cells expressing the tsA T antigen (BALB 58 cells) grow at 34 degrees C in either PDGF or 1% serum but not in IGF-1. At the restrictive temperature (39.6 degrees C), these cells can only grow in 10% serum. We show that BALB 58 cells, at 34 degrees C, have a markedly increased expression of IGF-1 and IGF-1 mRNA and that their growth in 1% serum (at 34 degrees C) is inhibited by an antisense oligodeoxynucleotide to the IGF-1 receptor RNA. When this tsA plasmid is stably transfected into cells constitutively overexpressing the human IGF-1 receptor cDNA, the resulting cell lines show a constitutively phosphorylated IGF-1 receptor and grow in serum-free medium at 34 degrees C (but not at 39.6 degrees C). A functional SV40 T antigen also increases the expression of a plasmid in which the reporter luciferase gene is under the control of a rat IGF-1 promoter. We conclude (i) that the SV40 T antigen induces the expression of IGF-1 and IGF-1 mRNA, at least in part by a transcriptional mechanism, thus altering the growth factors requirements, and (ii) that, in BALB/c3t3 cells, the SV40 T antigen necessitates a functional IGF-1 receptor for its growth-stimulating effect in low serum (or PDGF).

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