Future Med Chem. 2016 Oct 14. [Epub ahead of print]
MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: role of Hsp90 acetylation.
Panella S1, Marcocci ME2, Celestino I1, Valente S3, Zwergel C3, Li Puma DD4, Nencioni L2, Mai A5, Palamara AT1,6, Simonetti G2.
Author information
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 Heat shock protein 90 (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.
KEYWORDS:
HDAC inhibitors; HDACs; Hsp90; antiviral agents; influenza A virus; lysine acetylation
PMID: 27739328 DOI: 10.4155/fmc-2016-0073
[PubMed - as supplied by publisher]
MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: role of Hsp90 acetylation.
Panella S1, Marcocci ME2, Celestino I1, Valente S3, Zwergel C3, Li Puma DD4, Nencioni L2, Mai A5, Palamara AT1,6, Simonetti G2.
Author information
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 Heat shock protein 90 (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.
KEYWORDS:
HDAC inhibitors; HDACs; Hsp90; antiviral agents; influenza A virus; lysine acetylation
PMID: 27739328 DOI: 10.4155/fmc-2016-0073
[PubMed - as supplied by publisher]