MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: Role of Hsp90 acetylation

Simona Panella, Maria Elena Marcocci, Ignacio Celestino, Sergio Valente, Clemens Zwergel, Domenica Donatella Li Puma, Lucia Nencioni, Antonello Mai, Anna Teresa Palamara, Giovanna Simonetti

Research output: Contribution to journalArticle

Abstract

Aim: Histone deacetylases (HDACs) regulate the life cycle of several viruses. We investigated the ability of different HDAC inhibitors, to interfere with influenza virus A/Puerto Rico/8/34/H1N1 (PR8 virus) replication in Madin-Darby canine kidney and NCI cells. Results: 3-(5-(3-Fluorophenyl)-3-oxoprop-1-en-1-yl)-1-methyl-1H-pyrrol-2-yl)-N-hydroxyacrylamide (MC1568) inhibited HDAC6/8 activity and PR8 virus replication, with decreased expression of viral proteins and their mRNAs. Such an effect may be related to a decrease in intranuclear content of viral polymerases and, in turn, to an early acetylation of Hsp90, a major player in their nuclear import. Later, the virus itself induced Hsp90 acetylation, suggesting a differential and time-dependent role of acetylated proteins in virus replication. Conclusion: The inhibition of HDAC6/8 activity during early steps of PR8 virus replication could lead to novel anti-influenza strategy.

Original languageEnglish
Pages (from-to)2017-2031
Number of pages15
JournalFuture Medicinal Chemistry
Volume8
Issue number17
DOIs
Publication statusPublished - Nov 1 2016

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Keywords

  • antiviral agents
  • HDAC inhibitors
  • HDACs
  • Hsp90
  • influenza A virus
  • lysine acetylation

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

Cite this

Panella, S., Marcocci, M. E., Celestino, I., Valente, S., Zwergel, C., Li Puma, D. D., Nencioni, L., Mai, A., Palamara, A. T., & Simonetti, G. (2016). MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: Role of Hsp90 acetylation. Future Medicinal Chemistry, 8(17), 2017-2031. https://doi.org/10.4155/fmc-2016-0073