MC1568 inhibits HDAC6/8 activity and influenza A virus replication in lung epithelial cells: role of Hsp90 acetylation

Author:

Panella Simona1,Marcocci Maria Elena2,Celestino Ignacio1,Valente Sergio3,Zwergel Clemens3,Li Puma Domenica Donatella4,Nencioni Lucia2,Mai Antonello5,Palamara Anna Teresa16,Simonetti Giovanna2

Affiliation:

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.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3