TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro
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 concen...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1284439/full |
| _version_ | 1797434989429653504 |
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| author | Juanbin Yin Juanbin Yin Shasha Wang Shanhui Ren Zhengji Liang Junwei Ge Yuefeng Sun Xiangping Yin Xiangwei Wang |
| author_facet | Juanbin Yin Juanbin Yin Shasha Wang Shanhui Ren Zhengji Liang Junwei Ge Yuefeng Sun Xiangping Yin Xiangwei Wang |
| author_sort | Juanbin Yin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T10:40:49Z |
| format | Article |
| id | doaj.art-97e8d0061f5f4af195d2d1d0bef77c4f |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-09T10:40:49Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-97e8d0061f5f4af195d2d1d0bef77c4f2023-12-01T14:30:58ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-12-011410.3389/fmicb.2023.12844391284439TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitroJuanbin Yin0Juanbin Yin1Shasha Wang2Shanhui Ren3Zhengji Liang4Junwei Ge5Yuefeng Sun6Xiangping Yin7Xiangwei Wang8State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaDepartment of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaDepartment of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaState Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaTMP269, 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.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1284439/fullhistone deacetylase inhibitorTMP269rabies virus (RABV)antiviralautophagy |
| spellingShingle | Juanbin Yin Juanbin Yin Shasha Wang Shanhui Ren Zhengji Liang Junwei Ge Yuefeng Sun Xiangping Yin Xiangwei Wang TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro Frontiers in Microbiology histone deacetylase inhibitor TMP269 rabies virus (RABV) antiviral autophagy |
| title | TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro |
| title_full | TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro |
| title_fullStr | TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro |
| title_full_unstemmed | TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro |
| title_short | TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro |
| title_sort | tmp269 a small molecule inhibitor of class iia hdac suppresses rabv replication in vitro |
| topic | histone deacetylase inhibitor TMP269 rabies virus (RABV) antiviral autophagy |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1284439/full |
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