Simona Panella1, Maria Elena Marcocci2, Ignacio Celestino1, Sergio Valente3, Clemens Zwergel3, Domenica Donatella Li Puma4, Lucia Nencioni2, Antonello Mai5, Anna Teresa Palamara1,6, Giovanna Simonetti2. 1. San Raffaele Pisana Scientific Institute for Research, Hospitalization & Health Care, Telematic University, 00163 Rome, Italy. 2. Department of Public Health & Infectious Diseases, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy. 3. Department of Drug Chemistry & Technologies, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy. 4. Institute of Human Physiology, Medical School, Università Cattolica, 00168 Rome, Italy. 5. Department of Drug Chemistry & Technologies, Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy. 6. Department of Public Health & Infectious Diseases, Istituto Pasteur Italia-Fondazione Cenci Bolognetti, 'Sapienza' University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
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.
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.
Authors: Aaron Kolski-Andreaco; Corina M Balut; Claudia A Bertuccio; Annette S Wilson; William M Rivers; Xiaoning Liu; Robin E Gandley; Adam C Straub; Michael B Butterworth; David Binion; Daniel C Devor Journal: Am J Physiol Cell Physiol Date: 2022-01-19 Impact factor: 4.249
Authors: Roberta Mazzone; Clemens Zwergel; Marco Artico; Samanta Taurone; Massimo Ralli; Antonio Greco; Antonello Mai Journal: Clin Epigenetics Date: 2019-02-26 Impact factor: 6.551