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.
Acknowledgements
The authors thank M Aleandri and R Piacentini for their technical support during microscopy and image analysis.
Financial & competing interests disclosure
This research was financially supported by the Italian Ministry of Instruction Research PON 0101802 grant (AT Palamara), PRIN 2010PHT9NF005 grant (L Nencioni), FIRB RBFR10ZJQT grant (A Mai), RF-2010–2318330 (A Mai) grant, IIT-Sapienza Project (A Mai), and FP7 Projects BLUEPRINT/282510 and A-PARADDISE/602080 (A Mai). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.