Oncogenic Transformation of Hamster Embryo Cells in vitro by Adenovirus Type 5

Jf, Williams

doi:10.1038/243162a0

Cited by 79 publications

(36 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The typical multiplicity of infection was 10 plaque-forming units (pfu)͞ml. To analyze the growth characteristics of recombinant versus WT viruses, infections were performed at both 0.5 and 10 pfu͞ml, and plaque assays were performed as described (36).…”

Section: Cells and Virusesmentioning

confidence: 99%

Viral DNA synthesis-dependent titration of a cellular repressor activates transcription of the human adenovirus type 2 IVa ₂ gene

Iftode

Flint²

2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Synthesis of progeny DNA genomes in cells infected by human subgroup C adenoviruses leads to several changes in viral gene expression. These changes include transcription from previously silent, late promoters, such as the IV a2 promoter, and a large increase in the efficiency of major-late (ML) transcription. Some of these changes appear to take place sequentially, because the product of the IV a2 gene has been implicated in stimulation of ML transcription. Our previous biochemical studies suggested that IV a2 transcription is regulated by viral DNA synthesis-dependent relief of transcriptional repression by a cellular protein that we termed IV a2-RF. To test the relevance of such a repressor-titration mechanism during the viral infectious cycle, we introduced into the endogenous IV a2 promoter two mutations that impair in vitrobinding of IV a2-RF, but introduce no change (Rep7) or one conservative amino acid substitution (Rep6) into the overlapping coding sequence for the viral DNA polymerase. The results of run-on transcription assays indicated that both mutations induced earlierthan-normal and more efficient IV a2 transcription. Both mutations were also observed to result in modest increases in the efficiency of viral DNA synthesis. However, measurement of the concentration of IV a2 transcripts as a function of IVa2 template concentration demonstrated that the Rep mutations increased by up to 60-fold the efficiency with which IV a2 templates were used during the initial period of the late phase of infection, as predicted by the repressor titration hypothesis. These mutations also increased the efficiency of ML transcription in infected cells.late transcription ͉ repressor titration T he infectious cycles of animal viruses with DNA genomes are characterized by transcription of viral genes in a stereotyped temporal sequence, regardless of whether transcription is carried out by cellular or viral DNA-dependent RNA polymerases. The complexity of such temporal regulation of transcription increases with viral genome size. Nevertheless, transcription of viral late genes encoding structural proteins invariably depends on synthesis of progeny viral DNA genomes in the infected cell (reviewed in ref. 1). In some cases, the activities of a single viral protein control both viral DNA synthesis and late gene transcription. For example, the simian virus 40 early protein large T antigen is not only the origin-recognition protein required for initiation of viral DNA synthesis but also an activator of late transcription (see refs. 2-5). The transition from the early to the late transcriptional program is considerably more intricate in cells infected by DNA viruses with larger genomes, such as human adenoviruses.Synthesis of viral DNA in cells infected by human subgroup C adenoviruses, such as adenovirus type 2 or 5 (Ad2 or Ad5), results in transcription by cellular RNA polymerase II from three previously inactive viral promoters, those of the IX and IVa 2 genes and the E2 late promoter (reviewed in ref. 6) Such off-to-on swit...

show abstract

Section: Cells and Virusesmentioning

confidence: 99%

Viral DNA synthesis-dependent titration of a cellular repressor activates transcription of the human adenovirus type 2 IVa ₂ gene

Iftode

Flint²

2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In monkey cells the infection may be abortive or persistent (Baum, 1977), and abortive infections of rodent cells are associated with transformation. Thus transformed hamster cells arise from an abortive, though mainly lytic infection by Ad I2 (Strohl et aL I97O), or when the usually permissive infection by Ad 5 is rendered abortive by the use of temperaturesensitive (ts) mutants at the restrictive temperature (Williams, 1973) or of fragmented, but not intact, virus DNA (Graham et aL I975). Similarly, transformed rat embryo cells grow out from the abortively-infected survivors of a 'semi-permissive' infection by group C adenoviruses (Gallimore, 1974).…”

Section: Introductionmentioning

confidence: 99%

Infection of Mouse Liver by Human Adenovirus Type 5

Duncan¹,

Gordon²,

Gregory³

et al. 1978

Journal of General Virology

110

View full text Add to dashboard Cite

SUMMARYCBA mice, inoculated intravenously with large doses of adenovirus type 5, showed raised levels of serum aspartate aminotransferase (SAAT; EC 2.6.1.1) and died within a few days from histologically demonstrable hepatic necrosis. After inoculation of I LDs0, virus was rapidly taken up by the tissues where infectivity then declined greatly. Organ titres then increased about Ioo-fold by 48 h p.i. but, in the liver, which showed intranuclear inclusion bodies, and by electron microscopy, scattered intranuclear and intracytoplasmic adenovirions, the increase was IOOOO-to iooooo-fold. P antigen was detected by single radial diffusion in liver extracts, and by immunofluorescence in 80 % of liver cells at 36 h p.i. Hexon, penton base and fibre antigens appeared later and in fewer cells. The maximum amount of hexon, of demonstrable type 5 specificity, was shown by radioimmunoassay to be equivalent to up to 5 x io 11 whole adenovirions/g liver. It is concluded that human adenovirus type 5 undergoes an abortive but lytic infection in most liver cells but that replication may proceed to completion in a few.

show abstract

“…In an attempt to identify the 56K and 72K proteins in the infected extract, [14C]NAD-labelled $200 extracts were immunoprecipitated with adenovirus type 5 HT14b hamster tumour serum (Williams, 1973) followed by SDS-PAGE and autoradiography. Fig.…”

Section: Discussionmentioning

confidence: 99%

ADP-ribosylation in in vitro Systems Synthesizing Adenovirus DNA

Goding¹,

Shaw²,

Blair³

et al. 1983

Journal of General Virology

View full text Add to dashboard Cite

Oncogenic Transformation of Hamster Embryo Cells in vitro by Adenovirus Type 5

Cited by 79 publications

References 6 publications

Viral DNA synthesis-dependent titration of a cellular repressor activates transcription of the human adenovirus type 2 IVa ₂ gene

Viral DNA synthesis-dependent titration of a cellular repressor activates transcription of the human adenovirus type 2 IVa ₂ gene

Infection of Mouse Liver by Human Adenovirus Type 5

ADP-ribosylation in in vitro Systems Synthesizing Adenovirus DNA

Contact Info

Product

Resources

About

Oncogenic Transformation of Hamster Embryo Cells in vitro by Adenovirus Type 5

Cited by 79 publications

References 6 publications

Viral DNA synthesis-dependent titration of a cellular repressor activates transcription of the human adenovirus type 2 IVa 2 gene

Viral DNA synthesis-dependent titration of a cellular repressor activates transcription of the human adenovirus type 2 IVa 2 gene

Infection of Mouse Liver by Human Adenovirus Type 5

ADP-ribosylation in in vitro Systems Synthesizing Adenovirus DNA

Contact Info

Product

Resources

About

Viral DNA synthesis-dependent titration of a cellular repressor activates transcription of the human adenovirus type 2 IVa ₂ gene

Viral DNA synthesis-dependent titration of a cellular repressor activates transcription of the human adenovirus type 2 IVa ₂ gene