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 

机构地区：[1]CAS Key Laboratory of Molecular Virology and Immunology,Institute Pasteur of Shanghai,Chinese Academy of Sciences,University of the Chinese Academy of Sciences,Shanghai 200031,China [2]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Virologica Sinica》2021年第6期1352-1362,共11页中国病毒学（英文版）

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)。

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.

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

分 类 号：R373[医药卫生—病原生物学]