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

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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

16 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)2017-2031
Numero di pagine15
RivistaFuture Medicinal Chemistry
Volume8
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

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

Fingerprint

Entra nei temi di ricerca di 'MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: Role of Hsp90 acetylation'. Insieme formano una fingerprint unica.

Cita questo