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African swine fever virus-induced DNA polymerase is resistant to aphidicolin

M I Marques1, J V Costa

  • 1Gulbenkian Institute of Science, Oeiras, Portugal.

Virology
|November 1, 1992
PubMed

Insights

African swine fever virus (ASFV) DNA polymerase is uniquely resistant to aphidicolin, unlike other viral DNA polymerases. This resistance impacts viral DNA replication strategies and inhibitor development.

Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • African swine fever virus (ASFV) encodes a unique DNA polymerase.
  • Most alpha-like DNA polymerases of DNA viruses are inhibited by aphidicolin.

Purpose of the Study:

  • To investigate the sensitivity of ASFV DNA polymerase to aphidicolin.
  • To understand the implications of this resistance for viral DNA replication.

Main Methods:

  • In vivo studies assessing virus production and DNA synthesis inhibition by aphidicolin.
  • In vitro assays measuring ASFV DNA polymerase activity in the presence of inhibitors.
  • Analysis of ASFV mutants resistant to phosphonoacetic acid.

Main Results:

  • ASFV DNA polymerase is resistant to aphidicolin, with no effect on virus production or plaquing efficiency.
  • Viral DNA synthesis showed moderate inhibition only when aphidicolin was added immediately post-adsorption.
  • In vitro assays confirmed aphidicolin's lack of effect on ASFV DNA polymerase activity, independent of dCTP concentration.
  • Phosphonoacetic acid strongly inhibited both in vivo and in vitro ASFV DNA polymerase activity.
  • ASFV mutants resistant to phosphonoacetic acid also exhibited aphidicolin resistance.

Conclusions:

  • ASFV DNA polymerase exhibits intrinsic resistance to aphidicolin.
  • An early phase of ASFV DNA replication, potentially catalyzed by a different enzyme, is sensitive to aphidicolin.
  • This unique resistance profile has implications for understanding ASFV replication and developing antiviral strategies.

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