TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro

Juanbin Yin; Juanbin Yin; Shasha Wang; Shanhui Ren; Zhengji Liang; Junwei Ge; Yuefeng Sun; Xiangping Yin; Xiangwei Wang

doi:10.3389/fmicb.2023.1284439

Frontiers in Microbiology (Dec 2023)

TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro

Juanbin Yin,
Juanbin Yin,
Shasha Wang,
Shanhui Ren,
Zhengji Liang,
Junwei Ge,
Yuefeng Sun,
Xiangping Yin,
Xiangwei Wang

Affiliations

Juanbin Yin: State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Juanbin Yin: Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, China
Shasha Wang: State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Shanhui Ren: State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Zhengji Liang: State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Junwei Ge: Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, China
Yuefeng Sun: State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Xiangping Yin: State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Xiangwei Wang: State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China

DOI: https://doi.org/10.3389/fmicb.2023.1284439
Journal volume & issue: Vol. 14

Abstract

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TMP269, a small molecular inhibitor of IIa histone deacetylase, plays a vital role in cancer therapeutic. However, the effect of TMP269 on the regulation of viral replication has not been studied. In the present study, we found that TMP269 treatment significantly inhibited RABV replication at concentrations without significant cytotoxicity in a dose-dependent manner. In addition, TMP269 can reduce the viral titers and protein levels of RABV at an early stage in the viral life cycle. RNA sequencing data revealed that immune-related pathways and autophagy-related genes were significantly downregulated after RABV infection treated with TMP269. Further exploration shows that autophagy enhances RABV replication in HEK-293T cells, while TMP269 can inhibit autophagy to decrease RABV replication. Together, these results provide a novel treatment strategy for rabies.

Published in Frontiers in Microbiology

ISSN: 1664-302X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.frontiersin.org/journals/microbiology

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