Herpes Simplex Virus and Human Cytomegalovirus: Their Role in Morphological Transformation and Genital Cancers

Macnab, J. C. M.

doi:10.1099/0022-1317-68-10-2525

Cited by 71 publications

(32 citation statements)

References 63 publications

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“…Inhibition of methylation cannot be explained by an absence of DNA methyltransferase as the activity of this enzyme did not change during the early period of infection. Inhibition of host cell DNA methylation may be an important step in the transformation of cells by herpesviruses, and various transformed cell lines tested showed reduced levels of DNA methylation.It has been recognized since 1971 (12) Our interest in the induction of morphological transformation continues from our findings that transformed cells all react with antisera raised against HSV-infected cells (9,26,27 have shown that treatment of mouse embryo fibroblasts with the demethylating agent 5-azacytidine can lead to cell transformation.In this communication, we present evidence for the hypomethylation of DNA in a number of cell lines derived from foci morphologically transformed by HSV type 1 (HSV-1) or by the DNA from the transforming region of HSV-2 (the BglII N fragment). To demonstrate that this event is initiated by virus infection, we also report on the hypomethylation of host cell DNA synthesized during HSV-2 infection of primary rat embryo cells and provide evidence for the limited reincorporation of methylcytosine from degraded cellular DNA into viral DNA.…”

mentioning

confidence: 87%

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Hypomethylation of host cell DNA synthesized after infection or transformation of cells by herpes simplex virus.

Macnab¹,

Adams²,

Rinaldi³

et al. 1988

Mol. Cell. Biol.

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Infection of rat embryo cells with herpes simplex virus type 2 caused undermethylation of host cell DNA synthesized during infection. DNA made prior to infection was not demethylated, but some of its degradation products, including methyl dCMP, were incorporated into viral DNA. The use of mutant virus showed that some viral DNA synthesis appears to be required for the inhibition of methylation. Inhibition of methylation cannot be explained by an absence of DNA methyltransferase as the activity of this enzyme did not change during the early period of infection. Inhibition of host cell DNA methylation may be an important step in the transformation of cells by herpesviruses, and various transformed cell lines tested showed reduced levels of DNA methylation.It has been recognized since 1971 (12) Our interest in the induction of morphological transformation continues from our findings that transformed cells all react with antisera raised against HSV-infected cells (9,26,27 have shown that treatment of mouse embryo fibroblasts with the demethylating agent 5-azacytidine can lead to cell transformation.In this communication, we present evidence for the hypomethylation of DNA in a number of cell lines derived from foci morphologically transformed by HSV type 1 (HSV-1) or by the DNA from the transforming region of HSV-2 (the BglII N fragment). To demonstrate that this event is initiated by virus infection, we also report on the hypomethylation of host cell DNA synthesized during HSV-2 infection of primary rat embryo cells and provide evidence for the limited reincorporation of methylcytosine from degraded cellular DNA into viral DNA. MATERIALS AND METHODSBiological materials. Rat embryo control cells were prepared from 18-day-old embryos of the Hooded Lister rat (9). Rat embryo Asyn+C cells are rat embryo cells transformed at nonpermissive temperature with the HSV-1 strain 17 temperature-sensitive, (ts) mutant tsA with morphology of syn+. C designates the clone. Bn3 and Bn5 are two different clones of cells transformed after transfection of the BglII N fragment of HSV-2 strain HG52 which encodes the small subunit of ribonucleotide reductase activity and initiates morphological transformation (9). Bn5T is a tumor cell line derived after injection of Bn5 cells into inbred Hooded Lister rats. Cells were grown in BHKC13 medium supplemented with glutamine and 10% fetal calf serum (all from GIBCO Biocult, Paisley, U.K.

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mentioning

confidence: 87%

“…It has been recognized since 1971 (12) Our interest in the induction of morphological transformation continues from our findings that transformed cells all react with antisera raised against HSV-infected cells (9,26,27 have shown that treatment of mouse embryo fibroblasts with the demethylating agent 5-azacytidine can lead to cell transformation.…”

mentioning

confidence: 87%

Hypomethylation of host cell DNA synthesized after infection or transformation of cells by herpes simplex virus.

Macnab¹,

Adams²,

Rinaldi³

et al. 1988

Mol. Cell. Biol.

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“…In parallel with the seroepidemiology and with the search for virus DNA in tumours, numerous experiments have been performed to determine the oncogenic potential of HCMV by transformation studies in cell culture (reviewed by Macnab, 1987). The virus resembles oncogenic DNA viruses in its ability to stimulate host cell DNA synthesis (St. Jeor et al, 1974), transcription and cellular enzyme activities (Isom, 1979).…”

Section: Regulatory Elements In the Ie1 Upstream Regionmentioning

confidence: 99%

Human Cytomegalovirus: Recent Aspects from Molecular Biology

Mach

Stamminger

Jahn

1989

Journal of General Virology

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“…In conclusion, the main object of this paper is to draw attention to perhaps not unimportant phenomena in the scenario of herpesvirus action and to stimulate discussions on the biological relevance of herpesvirus-caused alterations of cellular DNA (Galloway & McDougall, 1983;Macnab, 1987;zur Hausen, 1983). …”

Section: Amplification Of Plasmids In Bhk Cells Infected With Hsvmentioning

confidence: 99%

Herpes Simplex Virus Causes Amplification of Recombinant Plasmids Containing Simian Virus 40 Sequences

Matz

1989

Journal of General Virology

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SUMMARYSimian virus 40 (SV40) DNA, inserted into a plasmid vector, does not replicate when transfected into baby hamster kidney cells. However, when the recipient cells are superinfected with herpes simplex virus type 1 (HSV-1), extensive amplification of the introduced plasmid occurs. Deletion of the late SV40 region or part of the coding sequences of the small tumour (t) antigen has no effect on the efficiency of amplification, whereas manipulations affecting either the SV40 origin of replication or the integrity of large tumour (T) antigen substantially decrease HSV-induced amplification. Phosphonoacetic acid, an inhibitor of HSV DNA polymerase, strongly inhibits plasmid replication. Also, an HSV-1 mutant with a temperature-sensitive defect in the DNA polymerase gene (tsH) is unable to carry out amplification of test plasmids at the non-permissive temperature. On the other hand, a further mutant (tsS) causes SV40-plasmid amplification independent of the temperature, but this mutant fails to amplify a plasmid with an HSV origin at the non-permissive temperature. Thus, HSV-induced amplification of heterologous DNA is possible in the absence of HSV DNA replication. Since tsS putatively has a defect in the gene coding for an HSV origin-binding protein (UL9), this observation appears plausible. The implications for interaction between herpesviral replication functions and heterologous (possibly cellular) DNA sequences are discussed. INTRODUCTIONInfection with herpes simplex virus (HSV) turns off the DNA replication of the host cell (Fenwick & Walker, 1978). It is, therefore, surprising that in several simian virus 40 (SV40)-transformed cell lines, SV40 DNA sequences are over-replicated upon HSV infection (Schlehofer et al., 1983(Schlehofer et al., , 1986Matz et al., 1984Matz et al., , 1985. This specific DNA amplification has been shown to depend on the herpesviral DNA polymerase (Matz et al., 1984). The structure of amplified SV40 DNA in the Syrian hamster cell line Elona has been analysed and found to consist of large concatemeric molecules (Matz, 1987). The structural similarity of the amplified DNA species with herpesviral DNA from defective interfering particles (Frenkel, 1981) supported the assumption that this illegitimate over-replication occurs under the direction of herpesviral DNA replication functions. Analysis of the amplified SV40 DNA revealed minor differences from standard SV40 DNA and failed to identify any sequence element that resembled a herpesvirus-specific origin of replication (Matz, 1987). In this report the question was addressed as to whether amplified DNA, isolated from the HSV-infected Elona cell line, or simply standard SV40 DNA can substitute for a herpesviral origin of replication in a functional assay previously designed for the identification of HSV replication origins (Stow, 1982).

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Herpes Simplex Virus and Human Cytomegalovirus: Their Role in Morphological Transformation and Genital Cancers

Cited by 71 publications

References 63 publications

Hypomethylation of host cell DNA synthesized after infection or transformation of cells by herpes simplex virus.

Hypomethylation of host cell DNA synthesized after infection or transformation of cells by herpes simplex virus.

Human Cytomegalovirus: Recent Aspects from Molecular Biology

Herpes Simplex Virus Causes Amplification of Recombinant Plasmids Containing Simian Virus 40 Sequences

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