Adenosine N1-oxide inhibits vaccinia virus replication by blocking translation of viral early mRNAs

E. M. Kane, S. Shuman

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Adenosine N1-oxide (ANO) is a potent and highly selective inhibitor of vaccinia virus replication. We examined the impact of ANO on vaccinia virus macromolecular synthesis during synchronous infection of BSC40 cells. Vital DNA replication and viral late protein synthesis were blocked completely by ANO, effects that were attributable to a defect in the expression of viral early genes. Vaccinia virus early proteins were not synthesized in the presence of ANO, even though vaccinia virus early mRNAs were produced. Cellular protein synthesis was unaffected by ANO, and virus infection in the presence of the drug did not elicit the normal shutoff of host protein synthesis. Adenosine N1-oxide triphosphate (ANO-TP), the predominant metabolite of the drug in vivo, could substitute for ATP in RNA synthesis by purified vaccinia virus RNA polymerase. ANO-TP could support early transcription by purified virions if dATP was provided as an energy source. ANO-TP did not inhibit early transcription in the presence of ATP. These findings suggest a novel antiviral mechanism whereby incorporation of a modified nucleotide into vital mRNAs might selectively block viral gene expression at the level of translation. We believe that ANO merits consideration as an antipoxvirus drug for topical treatment of molluscum contagiosum in humans.

Original languageEnglish (US)
Pages (from-to)6352-6358
Number of pages7
JournalJournal of Virology
Volume69
Issue number10
StatePublished - 1995

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Vaccinia virus
adenosine
Virus Replication
virus replication
translation (genetics)
oxides
Messenger RNA
Viral Genes
protein synthesis
drugs
Adenosine Triphosphate
Molluscum Contagiosum
Pharmaceutical Preparations
transcription (genetics)
Proteins
adenosine N(1)-oxide
Viral Proteins
Virus Diseases
synthesis
DNA-Directed RNA Polymerases

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

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abstract = "Adenosine N1-oxide (ANO) is a potent and highly selective inhibitor of vaccinia virus replication. We examined the impact of ANO on vaccinia virus macromolecular synthesis during synchronous infection of BSC40 cells. Vital DNA replication and viral late protein synthesis were blocked completely by ANO, effects that were attributable to a defect in the expression of viral early genes. Vaccinia virus early proteins were not synthesized in the presence of ANO, even though vaccinia virus early mRNAs were produced. Cellular protein synthesis was unaffected by ANO, and virus infection in the presence of the drug did not elicit the normal shutoff of host protein synthesis. Adenosine N1-oxide triphosphate (ANO-TP), the predominant metabolite of the drug in vivo, could substitute for ATP in RNA synthesis by purified vaccinia virus RNA polymerase. ANO-TP could support early transcription by purified virions if dATP was provided as an energy source. ANO-TP did not inhibit early transcription in the presence of ATP. These findings suggest a novel antiviral mechanism whereby incorporation of a modified nucleotide into vital mRNAs might selectively block viral gene expression at the level of translation. We believe that ANO merits consideration as an antipoxvirus drug for topical treatment of molluscum contagiosum in humans.",
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Adenosine N1-oxide inhibits vaccinia virus replication by blocking translation of viral early mRNAs. / Kane, E. M.; Shuman, S.

In: Journal of Virology, Vol. 69, No. 10, 1995, p. 6352-6358.

Research output: Contribution to journalArticle

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