Antiviral Effects of Aphidicolin, a New Antibiotic Produced by
            <i>Cephalosporium aphidicola</i>

Bucknall, R. A.; Moores, H.; Simms, Rebecca; Hesp, Barrie

doi:10.1128/aac.4.3.294

Cited by 144 publications

(76 citation statements)

References 6 publications

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“…The drug inhibits cell division, cellular DNA synthesis and repair replication in a number of manmmalian cells without affecting RNA synthesis or protein synthesis (2,3,4). The multiplication of herpes virus, vaccinia virus and SV40 is also sensitive to aphidicolin (1,4,20). Recently it has been reported that DNA polymerase a from various sources is strongly inhibited by low concentrations of aphidicolin while DNA polymerase 0 and y are resistant to drua concentrations up to 10-3 M (2,3,4,5,17,20).…”

Section: Introductionmentioning

confidence: 99%

“…a tetracyclic terpenoid isolated from the fungus Cephalosporium Aphidicola (1). The drug inhibits cell division, cellular DNA synthesis and repair replication in a number of manmmalian cells without affecting RNA synthesis or protein synthesis (2,3,4).…”

Section: Introductionmentioning

confidence: 99%

“…The replication of the linear DNA of the human adenoviruses type 2 and ©) IRL Press Umlted, 1 Falconberg Court, London W1V 5FG, U.K. that differs from that of cellular or papovavirus DNA. Adenovirus DNA replication starts at one of the molecular ends and proceeds unidirectionally by a strand displacement mechanism whereas papovavirus DNA replicates bidirectionally, both parental strands being duplicated almost synchronously (review, see 7,8).…”

Section: Introductionmentioning

confidence: 99%

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Differential effect of aphidicolin on adenovirus DNA synthesis and cellular DNA synthesis

Kwant

Vliet

1980

Nucl Acids Res

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There is strong evidence for a participation of DNA polymerase y in the replication of adenovirus (Ad) DNA. To study a possible additional role of DNA polymerase a we measured the effect of aphidicolin on viral DNA replication.In intact cells, aphidicolin inhibits Ad DNA synthesis weakly. The drug concentration required for 50% inhibition of Ad DNA replication was 300-400 fold higher than for a similar effect on cellular DNA synthesis. Such a differential inhibition was also observed in AGMK cells doubly infected with SV40 and the simian adenovirus SA7. No evidence was found for modification of aphidicolin in infected cells or for a change in aphidicolin sensitivity of DNA polymerase a after infection.The extent of inhibition of purified DNA polymerase a was dependent upon the dCTP concentration. The same situation was observed when DNA synthesis was studied in isolated nuclei from uninfected cells. However, in nuclei from Ad infected cells no effect of dCTP on aphidicolin sensitivity was found. These results were taken as evidence that DNA polymerase a does not participate in the replication of adenovirus DNA.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential effect of aphidicolin on adenovirus DNA synthesis and cellular DNA synthesis

Kwant

Vliet

1980

Nucl Acids Res

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“…To this end, we have used aphidicolin [16], a specific inhibitor of the a-like DNA polymerase of higher plant cells [17], as well as that of the DNA polymerase t~ of animal cells [4,6,9,18].…”

Section: Introduction 2 Materials and Methodsmentioning

confidence: 99%

DNA repair synthesis in plant protoplasts is aphidicolin‐resistant

Sala

Magnien

Galli³

et al. 1982

FEBS Letters

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“…Huberman, 1981) and this conclusion is not unexpected. In addition, there are previous reports of the inhibition of HSV growth (Bucknall et al, 1973) and DNA polymerase activity by aphidicolin (Pedrali-Noy & Spadari, 1979Dicioccio et al, 1980). However, detailed studies of the mode of action of this interesting inhibitor on cellular ~-polymerases are likely to be constrained by the difficulties of acquiring the relevant genetic information.…”

Section: Discussionmentioning

confidence: 99%

Single Mutations at Many Sites within the DNA Polymerase Locus of Herpes Simplex Viruses Can Confer Hypersensitivity to Aphidicolin and Resistance to Phosphonoacetic Acid

Honess

Purifoy

Young

et al. 1984

Journal of General Virology

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SUMMARYAphidicolin, a tetracyclic diterpenoid which inhibits the DNA polymerase-ct activities of many eukaryotic cells, inhibited herpes simplex virus growth and DNA synthesis in infected cultures and the activity of the virus DNA polymerase in vitro. A wide range of stable aphidicolin sensitivities was represented amongst a collection of virus strains with no prior exposure to this drug, but viruses with polymerase mutations selected for resistance to phosphonoacetic acid (PAA) or to acycloguanosine typically showed increased sensitivity to aphidicolin. Of 16 unrelated PAA-resistant variants, 7 were hypersensitive to aphidicolin. A number of mutants with temperature-sensitive (ts) lesions in the polymerase gene also showed increased aphidicolin sensitivity (e.g. HSV-I[mP17]tsH) or aphidicolin hypersensitivity (e.g. HSV-I[KOS]tsD9, tsC4).Resistance or hypersensitivity of virus growth and DNA synthesis in vivo were correlated with resistance or hypersensitivity of virus DNA polymerase reactions in vitro. Resistance phenotypes were closely linked to the polymerase gene during recombination with outside markers. Moreover, the selection of aphidicolin-resistant mutants from hypersensitive variants with independent PAA resistance or ts mutations in the polymerase gene could result in co-selection for PAA-sensitive and ts + phenotypes. Confirmation that multiple independent mutations could determine aphidicolin hypersensitivity was obtained by studies of recombination between independent hypersensitive variants. Aphidicolin-resistant recombinant progeny were formed with recombination frequencies (0.4 to 2.6~) compatible with intragenic events. With parental hypersensitive variants which were products of limited PAA selection, or with the ts polymerase mutations, aphidicolin-resistant recombinants were PAA-sensitive and/or ts +. The segregation of other markers (ts, plaque morphology) amongst recombinant progeny permitted the orientation of multiple determinants of PAA resistance and aphidicolin hypersensitivity with respect to other markers in the polymerase gene and in other genes. The nature of residues determined at any one of a constellation of separate sites within the polymerase locus can determine resistance or sensitivity to antiviral drugs and aphidicolin hypersensitivity associated with changes at the polymerase locus facilitates high resolution genetic analysis of this locus. INTRODUCTION Herpesviruses characteristically specify the synthesis of a novel DNA polymerase activity which is essential for the replication of virus DNA in productively infected cells. For herpes simplex viruses of type l and type 2 (HSV-1, HSV-2) there is now good evidence that t Present address:

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Antiviral Effects of Aphidicolin, a New Antibiotic Produced by Cephalosporium aphidicola

Cited by 144 publications

References 6 publications

Differential effect of aphidicolin on adenovirus DNA synthesis and cellular DNA synthesis

Differential effect of aphidicolin on adenovirus DNA synthesis and cellular DNA synthesis

DNA repair synthesis in plant protoplasts is aphidicolin‐resistant

Single Mutations at Many Sites within the DNA Polymerase Locus of Herpes Simplex Viruses Can Confer Hypersensitivity to Aphidicolin and Resistance to Phosphonoacetic Acid

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