TY - JOUR
T1 - MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells
T2 - Role of Hsp90 acetylation
AU - Panella, Simona
AU - Marcocci, Maria Elena
AU - Celestino, Ignacio
AU - Valente, Sergio
AU - Zwergel, Clemens
AU - Li Puma, Domenica Donatella
AU - Nencioni, Lucia
AU - Mai, Antonello
AU - Palamara, Anna Teresa
AU - Simonetti, Giovanna
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - antiviral agents
KW - HDAC inhibitors
KW - HDACs
KW - Hsp90
KW - influenza A virus
KW - lysine acetylation
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U2 - 10.4155/fmc-2016-0073
DO - 10.4155/fmc-2016-0073
M3 - Article
AN - SCOPUS:84994010342
VL - 8
SP - 2017
EP - 2031
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
SN - 1756-8919
IS - 17
ER -