Histone Deacetylase Inhibitor SAHA Induces Expression of Fatty Acid-Binding Protein 4 and Inhibits Replication of Human Cytomegalovirus

作     者：Zhongshun Liu Baoqin Xuan Shubing Tang Zhikang Qian Zhongshun Liu;Baoqin Xuan;Shubing Tang;Zhikang Qian

作者机构：CAS Key Laboratory of Molecular Virology and ImmunologyInstitute Pasteur of ShanghaiChinese Academy of SciencesUniversity of the Chinese Academy of SciencesShanghai 200031China University of Chinese Academy of SciencesBeijing 100049China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2021年第36卷第6期

页      面：1352-1362页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：This research was supported by National Key R&D Program of China Grant(2016YFA0502101) National Natural Science Foundation of China(grants 81371826 and 81572002 to Z.Q.,grants 31300148 and 31570169) 

主　　题：Histone deacetylases inhibitor(HDACI) Suberoylanilide hydroxamic acid(SAHA) Human cytomegalovirus(HCMV) Fatty acid-binding protein 4(FABP4) 

摘      要：Suberoylanilide hydroxamic acid(SAHA) is a histone deacetylase inhibitor that shows marked efficacy against many types of cancers and is approved to treat severe metastatic cutaneous T-cell lymphomas. In addition to its anticancer activity,SAHA has significant effects on the growth of many viruses. The effect of SAHA on replication of human cytomegalovirus(HCMV) has not, however, been investigated. Here, we showed that the replication of HCMV was significantly suppressed by treatment with SAHA at concentrations that did not show appreciable cytotoxicity. SAHA reduced transcription and protein levels of HCMV immediate early genes, showing that SAHA acts at an early stage in the viral life-cycle. RNAsequencing data mining showed that numerous pathways and molecules were affected by SAHA. Interferon-mediated immunity was one of the most relevant pathways in the RNA-sequencing data, and we confirmed that SAHA inhibits HCMV-induced IFN-mediated immune responses using quantitative Real-time PCR(qRT-PCR). Fatty acid-binding protein 4(FABP4), which plays a role in lipid metabolism, was identified by RNA-sequencing. We found that FABP4 expression was reduced by HCMV infection but increased by treatment with SAHA. We then showed that knockdown of FABP4 partially rescued the effect of SAHA on HCMV replication. Our data suggest that FABP4 contributes to the inhibitory effect of SAHA on HCMV replication.