Baculovirus Replication: Inhibition of Trichoplusia ni Multiple Nuclear Polyhedrosis Virus by [E]-5-(2-Bromovinyl)-2'-deoxyuridine

Wang, X.; Lescott, Thelma; Clercq, Erik De; Kelly, D. C.

doi:10.1099/0022-1317-64-6-1221

Cited by 9 publications

(5 citation statements)

References 15 publications

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“…In a previous study on the effect of BVdU on baculovirus replication (Wang et al, 1983) it was shown that both BVdU and its triphosphorylated derivative inhibited DNA polymerase activity in crude cell extracts, and the direct effect of BVdU on DNA polymerase activity was attributed to its phosphorylation by cell or viral deoxypyrimidine kinases present in the extract. By analogy with certain herpesviruses, only BVdU triphosphate should block DNA polymerase activity (De Clercq et al, 1980).…”

Section: Discussionmentioning

confidence: 99%

“…Aphidicolin, BVdU and BVdU triphosphate have been shown to inhibit both cell and virus-stimulated enzymes in crude and partially purified preparations (Miller et al, 1981;Wang et al, 1983). BVdU and aphidicolin both inhibit baculovirus replication (Wang et al, 1983;X.…”

Section: Identification Of Dna Polymerasementioning

confidence: 99%

“…A number of enzymes concerned with DNA synthesis are stimulated in baculovirus-infected cells including deoxypyrimidine kinase and DNA polymerase (Kelly, 1981(Kelly, , 1982Miller et al, 1981 ;Wang et al, 1983). Although the enzymes have not yet been shown to be virus-coded, the virus-stimulated enzymes differ in properties from the normal cell enzymes, and it is probable that the stimulated enzymes are virus-specified.…”

Section: Introductionmentioning

confidence: 99%

“…The enzyme activity is inhibited by aphidicolin and bromovinyldeoxyuridine triphosphate (Miller et al, 1981 ;Wang et al, 1983) and it was of interest to investigate the effect of these drugs on the purified enzyme, since drug-resistant mutants will probably help to elucidate baculovirus DNA replication.…”

Section: Introductionmentioning

confidence: 99%

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Baculovirus Replication: Purification and identification of the Trichoplusia ni Nuclear Polyhedrosis Virus-induced DNA Polymerase

Wang¹,

Kelly²

1983

Journal of General Virology

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SUMMARYDNA polymerase activity present in Trichoplusia ni multiple nucleocapsid nuclear polyhedrosis virus-infected Spodopterafrugiperda cells has been analysed by chromatography on DNA-cellulose and phosphocellulose columns. In infected cells a new fraction of activity was found to bind to the columns more strongly that did polymerase activity in uninfected cells. The infected-cell-specific DNA polymerase was purified by a combination of DNA-cellulose chromatography of crude extracts and phosphocellulose chromatography of the semi-purified activity. The final product contained a single polypeptide of molecular weight 126 000 which was not found in uninfected cells. The purified enzyme was inhibited by aphidicolin and [E]-5-(2-bromovinyl)-2'-deoxyuridine triphosphate, but not by bromovinyldeoxyuridine. The enzyme was shown to be an early enzyme, probably a delayed early protein, since it was present in cells inhibited by aphidicolin which were locked into the synthesis of early proteins by the drug.

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Section: Discussionmentioning

confidence: 99%

Section: Identification Of Dna Polymerasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Baculovirus Replication: Purification and identification of the Trichoplusia ni Nuclear Polyhedrosis Virus-induced DNA Polymerase

Wang¹,

Kelly²

1983

Journal of General Virology

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“…This class of compounds targets DNApol by mimicking and/or competing with the normal deoxynucleoside triphosphate (dNTP) substrates. Several inhibitors of baculovirus DNA replication have been documented, with the majority falling within this category, including, surprisingly, the antiretroviral drug abacavir (26,43,51). Of these, the effects of abacavir and aphidicolin on AcMNPV replication were reversible (43).…”

mentioning

confidence: 99%

Selection and Characterization of Autographa californica Multiple Nucleopolyhedrovirus DNA Polymerase Mutations

Feng

Thumbi

Jong

et al. 2012

J Virol

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c Autographa californica multiple nucleopolyhedrovirus (AcMNPV) DNA polymerase (DNApol) is essential for viral DNA replication. AcMNPV mutants resistant to aphidicolin, a selective inhibitor of viral DNA replication, and abacavir, an efficacious nucleoside analogue with inhibitory activity against reverse transcriptase, were selected by the serial passage of the parental AcMNPV in the presence of increasing concentrations of aphidicolin or abacavir. These drug-resistant mutants had either a single (C543R) (aphidicolin) or a double (C543R and S611T) (abacavir) point mutation within conserved regions II and III. To confirm the role of these point mutations in AcMNPV DNA polymerase, a dnapol knockout virus was first generated, and several repair viruses were constructed by transposing the dnapol wild-type gene or ones containing a single or double point mutation into the polyhedrin locus of the dnapol knockout bacmid. The single C543R or double C543R/S611T mutation showed increased resistance to both aphidicolin and abacavir and, even in the absence of drug, decreased levels of virus and viral DNA replication compared to the wild-type repair virus. Surprisingly, the dnapol mutant repair viruses led to the generation of occlusion-derived viruses with mostly single and only a few multiple nucleocapsids in the ring zone and within polyhedra. Thus, these point mutations in AcMNPV DNA polymerase increased drug resistance, slightly compromised virus and viral DNA replication, and influenced the viral morphogenesis of occlusion-derived virus.T he molecular mechanisms of baculovirus DNA replication have been studied in Autographa californica multiple nucleopolyhedrovirus (AcMNPV), the type species of the genus Alphabaculovirus of the family Baculoviridae. Baculoviruses are distinctive in that they have a biphasic replication cycle producing budded virions (BVs) early in infection, and later in infection, single or multiple nucleocapsids are enveloped in the ring zone to form occlusion-derived virus (ODV), which becomes embedded within polyhedra (14). AcMNPV replicates its large (134-kb), circular, double-stranded DNA genome (1) in the nucleus of infected cells following a molecular interaction between virus-encoded transacting factors and cis-acting DNA sequences. To date, the functional roles of only some trans-acting factors involved in DNA replication have been elucidated (24,31).The AcMNPV DNA polymerase (DNApol) plays an essential role in AcMNPV DNA replication (27,48). The 3-kb DNApol open reading frame (ORF) encodes a polypeptide of 984 amino acids (aa) with a predicted molecular mass of 114.31 kDa (46). Previous biochemical studies suggested that baculovirus-encoded DNApol is most closely related to ␣-and ␦-like DNApols of various DNA viruses, such as herpes simplex viruses (HSVs), adenoviruses, and poxviruses (18,30). Moreover, the AcMNPV DNApol is sensitive to aphidicolin, a feature common to ␣-like DNApols (18,37,43). The ␦-like (replicative-form) DNApol requires proliferating cell nuclear antigen (PCNA) (a proc...

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Synthetic pyrimidine nucleoside analogues

Clercq¹

1985

Approaches to Antiviral Agents

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Baculovirus Replication: Inhibition of Trichoplusia ni Multiple Nuclear Polyhedrosis Virus by [E]-5-(2-Bromovinyl)-2'-deoxyuridine

Cited by 9 publications

References 15 publications

Baculovirus Replication: Purification and identification of the Trichoplusia ni Nuclear Polyhedrosis Virus-induced DNA Polymerase

Baculovirus Replication: Purification and identification of the Trichoplusia ni Nuclear Polyhedrosis Virus-induced DNA Polymerase

Selection and Characterization of Autographa californica Multiple Nucleopolyhedrovirus DNA Polymerase Mutations

Synthetic pyrimidine nucleoside analogues

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