In vitro inhibition of African swine fever virus-topoisomerase II disrupts viral replication

作者: Ferdinando B. Freitas , Gonçalo Frouco , Carlos Martins , Alexandre Leitão , Fernando Ferreira

DOI: 10.1016/J.ANTIVIRAL.2016.08.021

关键词: BiologyTopoisomeraseAfrican swine fever virusVirusViral entryVirologyViral genome replicationTopoisomerase inhibitorViral replicationCytopathic effect

摘要: Abstract African swine fever virus (ASFV) is the etiological agent of a highly-contagious and fatal disease domestic pigs, leading to serious socio-economic impact in affected countries. To date, neither vaccine nor selective anti-viral drug are available for prevention or treatment (ASF), emphasizing need more detailed studies at role ASFV proteins involved viral DNA replication transcription. Notably, encodes functional type II topoisomerase (ASFV-Topo II) we recently showed that several fluoroquinolones (bacterial inhibitors) fully abrogate in vitro . Here, report ASFV-Topo gene actively transcribed throughout infection, with transcripts being detected as early 2 hpi reaching maximum peak concentration around 16 hpi, when synthesis, transcription translation active. siRNA knockdown experiments plays critical expression, transfected cells presenting lower (up 89% decrease) reduced cytopathic effect (−66%) compared control group. Further, significant decrease number both infected (75.5%) factories per cell yields 99.7%, 2.5 log) was found only targeting II. We also demonstrate short exposure enrofloxacin during late phase infection (from 15 1 hpi) induces fragmentation genomes, whereas no genomes were added from 2 16 hpi), suggesting poisons. Altogether, our results enzyme has an essential genome transcription, idea this can be potential target development against ASF.

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