Stimulation of cellular RNA synthesis in mouse-kidney cell cultures infected with SV40 virus

doi:10.1016/0014-4827(76)90175-0

Experimental Cell Research

Volume 100, Issue 2, July 1976, Pages 433-436

https://doi.org/10.1016/0014-4827(76)90175-0 Get rights and content

Abstract

In confluent primary mouse-kidney cell cultures, abortive infection with SV40 has been demonstrated to cause an increase in the bulk of cellular RNA (mainly rRNA). However, the increase in the rate of rRNA synthesis is not involved in the initiation of the virus-induced cellular DNA replication since after actinomycin D treatment (0.05 μg/ml, from 6 to 9 h p.i.) the onset of cellular DNA replication takes place at a time when the rate of rRNA synthesis is still depressed.

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Cited by (14)

Cell-type specific regulation of gene expression by simian virus 40 T antigens
2009, Virology
Citation Excerpt :
T antigen also enhances transcription dependent on RNA polymerases I and III and SV40 infected cells have higher levels of tRNA and rRNA synthesis than uninfected cells (Baserga et al., 1978; Felton-Edkins and White, 2002; Larminie et al., 1999; Sekiya and Oda, 1972; Zhai and Comai, 1999; Zhai et al., 1997). These observations are consistent with early reports indicating that global cellular transcription is increased upon SV40 infection (May et al., 1976; Oda and Dulbecco, 1968). Three other cellular proteins are known to bind to T antigen but their role in SV40 transformation is not firmly established.
SV40 transforms cells through the action of two oncoproteins, large T antigen and small t antigen. Small t antigen targets phosphatase PP2A, while large T antigen stimulates cell proliferation and survival by action on multiple proteins, including the tumor suppressors Rb and p53. Large T antigen also binds components of the transcription initiation complex and several transcription factors. We examined global gene expression in SV40-transformed mouse embryo fibroblasts, and in enterocytes obtained from transgenic mice. SV40 transformation alters the expression of approximately 800 cellular genes in both systems. Much of this regulation is observed in both MEFs and enterocytes and is consistent with T antigen action on the Rb-E2F pathway. However, the regulation of many genes is cell-type specific, suggesting that unique signaling pathways are activated in different cell types upon transformation, and that the consequences of SV40 transformation depends on the type of cell targeted.
SV40: Cell transformation and tumorigenesis
2009, Virology
Citation Excerpt :
However, these rare stable transformants are easily detected because after a few days of culture, their clonal descendants overgrow the monolayer to form dense foci. Infection with either SV40 or polyomavirus results in increased synthesis of cellular RNAs and proteins (Frearson et al., 1966; Kit et al., 1966, 1967b; May et al., 1976; Oda and Dulbecco, 1968; Winocour and Robbins, 1970). Furthermore, infection of either permissive or nonpermissive cells with these viruses stimulates quiescent cells to undergo several rounds of DNA synthesis (Gershon et al., 1965, 1966; Hatanaka and Dulbecco, 1966; Henry et al., 1966; Kit et al., 1967a; Winocour et al., 1965).
The story of SV40-induced tumorigenesis and cellular transformation is intimately entwined with the development of modern molecular biology. Because SV40 and other viruses have small genomes and are relatively easy to manipulate in the laboratory, they offered tractable systems for molecular analysis. Thus, many of the early efforts to understand how eukaryotes replicate their DNA, regulate expression of their genes, and translate mRNA were focused on viral systems. The discovery that SV40 induces tumors in certain laboratory animals and transforms many types of cultured cells offered the first opportunity to explore the molecular basis for cancer. The goal of this article is to highlight some of the experiments that have led to our current view of SV40-induced transformation and to provide some context as to how they contributed to basic research in molecular biology and to our understanding of cancer.
The mechanism of cell transformation by SV40 and Polyoma virus
1984, Pharmacology and Therapeutics
The role of large T antigen in simian virus 40-induced reactivation of silent rRNA genes in human-mouse hybrid cells
1980, Virology
In some hybrid cell lines between human and mouse cells the ribosomal RNA (rRNA) genes of both species are present but only the rRNA of the dominant species is expressed. The silent rRNA genes can be reactivated if the hybrid cells are infected with simian virus 40 (SV40). The role of the SV40 early gene, the A gene, in the reactivation of the silent rRNA genes was investigated. A temperature-sensitive mutant of the SV40 early region, tsA58, could not reactivate the silent mouse rRNA genes at the nonpermissive temperature of 39° in human > mouse hybrids, although it could do so at 32°. Wild-type SV40 did induce the expression of mouse rRNA at both 32° and 39°. Adenovirus 2 (Ad2) could not reactivate the silent rRNA genes in these hybrid cells. Infection by either Ad2+D−1 or Ad2+D−2, hybrid adenoviruses which contain portions of the A region of the SV40 genome, led to expression of both species of 28 S rRNA. However, infection by the nondefective adenovirus Ad2+ND-1 (H71), which contains an incomplete SV40 A region, failed to reactivate silent rRNA genes. Hybrid cells infected with the small t deletion mutant of SV40, dl-2005, also showed reactivation. Finally, both human and mouse rRNA were found in SV40-transformed mouse-human hybrid cells and in polyoma virus-infected hybrids. These results indicated that SV40 reactivation of silent rRNA genes in human-mouse hybrids requires the major product of the A gene, the large T antigen.
Viral 'tumor antigens' a novel type of mammalian regulator protein
1978, BBA - Reviews on Cancer
Stimulation of RNA synthesis in isolated nucleoli by preparations of simian virus 40 T antigen
1978, Virology
Partially purified and highly purified preparations of simian virus 40 (SV40) T antigen from SV80 cells stimulate the incorporation of [³H]UTP into RNA in isolated rat liver nucleoli. The increased incorporation is dependent on an endogenous a-amanitin-resistant RNA polymerase, and ribosomal RNA sequences are present in the product. T antigen was also partially purified from Chinese hamster cells transformed by a tsA mutant of SV40. The complement-fixing activity of tsT was rapidly inactivated by heating at 50°, and this inactivation was paralleled by a marked decrease in its ability to stimulate nucleolar RNA synthesis in vitro. Under these same conditions, T preparations from wild-type transformed cells were more resistant, in terms of both complement-fixing activity and ability to stimulate nucleolar RNA synthesis. The stimulation of nucleolar RNA synthesis with wild-type T preparations of different degrees of purity correlated with the ability of the preparations to fix complement, even with highly purified preparations. Finally, cellular RNA synthesis was also stimulated when quiescent 3T3 cells were infected with wild-type SV40. The results do not prove, but strongly suggest, that one of the sites of action of SV40 T antigen may be at the level of transcription of nucleolar DNA.

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Preliminary noteStimulation of cellular RNA synthesis in mouse-kidney cell cultures infected with SV40 virus

Abstract

J biol chem

Virology

Preliminary note
Stimulation of cellular RNA synthesis in mouse-kidney cell cultures infected with SV40 virus