Elsevier

Virology

Volume 493, June 2016, Pages 209-216
Virology

Functional characterization and inhibition of the type II DNA topoisomerase coded by African swine fever virus

https://doi.org/10.1016/j.virol.2016.03.023Get rights and content
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Highlights

  • ASFV pP1192R is active under conditions similar for other type II topoisomerases.

  • pP1192R catenates, decatenates and relaxes DNA, but does not supercoil relaxed DNA.

  • pP1192R׳s activity is processive.

  • Activity of pP1192R is inhibited by common topoisomerase II poisons and inhibitors.

  • Doxorubicin, coumermycin A1 and m-AMSA had the highest effect on pP1192R activity.

Abstract

DNA topoisomerases are essential for DNA metabolism and while their role is well studied in prokaryotes and eukaryotes, it is less known for virally-encoded topoisomerases. African swine fever virus (ASFV) is a nucleo-cytoplasmic large DNA virus that infects Ornithodoros ticks and all members of the family Suidae, representing a global threat for pig husbandry with no effective vaccine nor treatment. It was recently demonstrated that ASFV codes for a type II topoisomerase, highlighting a possible target for control of the virus. In this work, the ASFV DNA topoisomerase II was expressed in Saccharomyces cerevisiae and found to efficiently decatenate kDNA and to processively relax supercoiled DNA. Optimal conditions for its activity were determined and its sensitivity to a panel of topoisomerase poisons and inhibitors was evaluated. Overall, our results provide new knowledge on viral topoisomerases and on ASFV, as well as a possible target for the control of this virus.

Keywords

African swine fever virus
ASFV
P1192R
DNA Topoisomerases, Type II
Topoisomerase II inhibitors
Amsacrine
Doxorubicin
Ciprofloxacin

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