title: MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: role of Hsp90 acetylation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The inhibition of HDAC6/8 activity during early steps of PR8 virus replication could lead to novel anti-influenza strategy.
authors.affiliation: San Raffaele Pisana Scientific Institute for Research, Hospitalization & Health Care, Telematic University, 00163 Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Panella
authors.affiliation: Department of Public Health & Infectious Diseases, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Marcocci
authors.affiliation: San Raffaele Pisana Scientific Institute for Research, Hospitalization & Health Care, Telematic University, 00163 Rome, Italy.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Celestino
authors.affiliation: Department of Drug Chemistry & Technologies, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Valente
authors.affiliation: Department of Drug Chemistry & Technologies, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Clemens
authors.initials: C
authors.lastname: Zwergel
authors.affiliation: Institute of Human Physiology, Medical School, Università Cattolica, 00168 Rome, Italy.
authors.forename: Domenica Donatella
authors.initials: DD
authors.lastname: Li Puma
authors.affiliation: Department of Public Health & Infectious Diseases, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Nencioni
authors.affiliation: Department of Drug Chemistry & Technologies, Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
authors.affiliation: San Raffaele Pisana Scientific Institute for Research, Hospitalization & Health Care, Telematic University, 00163 Rome, Italy.|Department of Public Health & Infectious Diseases, Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Anna Teresa
authors.initials: AT
authors.lastname: Palamara
authors.affiliation: Department of Public Health & Infectious Diseases, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Simonetti
keywords: HDAC inhibitors; HDACs; Hsp90; antiviral agents; influenza A virus; lysine acetylation