Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation
Reversing HIV-1 latency promotes the killing of infected cells and is essential for cure strategies. However, current latency-reversing agents (LRAs) are not entirely effective and safe in activating latent viruses in patients. In this study, we investigated whether Scopoletin (6-Methoxy-7-hydroxyco...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/16/12649 |
| _version_ | 1797584504891637760 |
|---|---|
| author | Yuqi Zhu Zhengtao Jiang Lin Liu Xinyi Yang Min Li Yipeng Cheng Jianqing Xu Chunhua Yin Huanzhang Zhu |
| author_facet | Yuqi Zhu Zhengtao Jiang Lin Liu Xinyi Yang Min Li Yipeng Cheng Jianqing Xu Chunhua Yin Huanzhang Zhu |
| author_sort | Yuqi Zhu |
| collection | DOAJ |
| description | Reversing HIV-1 latency promotes the killing of infected cells and is essential for cure strategies. However, current latency-reversing agents (LRAs) are not entirely effective and safe in activating latent viruses in patients. In this study, we investigated whether Scopoletin (6-Methoxy-7-hydroxycoumarin), an important coumarin phytoalexin found in plants with multiple pharmacological activities, can reactivate HIV-1 latency and elucidated its underlying mechanism. Using the Jurkat T cell model of HIV-1 latency, we found that Scopoletin can reactivate latent HIV-1 replication with a similar potency to Prostratin and did so in a dose- and time-dependent manner. Moreover, we provide evidence indicating that Scopoletin-induced HIV-1 reactivation involves the nuclear factor kappa B (NF-κB) signaling pathway. Importantly, Scopoletin did not have a stimulatory effect on T lymphocyte receptors or HIV-1 receptors. In conclusion, our study suggests that Scopoletin has the potential to reactivate latent HIV-1 without causing global T-cell activation, making it a promising treatment option for anti-HIV-1 latency strategies. |
| first_indexed | 2024-03-10T23:52:36Z |
| format | Article |
| id | doaj.art-ae1b5014d48740e19d46a7ee07a0966e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:52:36Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ae1b5014d48740e19d46a7ee07a0966e2023-11-19T01:26:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161264910.3390/ijms241612649Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell ActivationYuqi Zhu0Zhengtao Jiang1Lin Liu2Xinyi Yang3Min Li4Yipeng Cheng5Jianqing Xu6Chunhua Yin7Huanzhang Zhu8State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaScientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, ChinaState Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaState Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology, Ministry of Education, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200438, ChinaReversing HIV-1 latency promotes the killing of infected cells and is essential for cure strategies. However, current latency-reversing agents (LRAs) are not entirely effective and safe in activating latent viruses in patients. In this study, we investigated whether Scopoletin (6-Methoxy-7-hydroxycoumarin), an important coumarin phytoalexin found in plants with multiple pharmacological activities, can reactivate HIV-1 latency and elucidated its underlying mechanism. Using the Jurkat T cell model of HIV-1 latency, we found that Scopoletin can reactivate latent HIV-1 replication with a similar potency to Prostratin and did so in a dose- and time-dependent manner. Moreover, we provide evidence indicating that Scopoletin-induced HIV-1 reactivation involves the nuclear factor kappa B (NF-κB) signaling pathway. Importantly, Scopoletin did not have a stimulatory effect on T lymphocyte receptors or HIV-1 receptors. In conclusion, our study suggests that Scopoletin has the potential to reactivate latent HIV-1 without causing global T-cell activation, making it a promising treatment option for anti-HIV-1 latency strategies.https://www.mdpi.com/1422-0067/24/16/12649ScopoletinHIV-1 latencyreactivationNF-κBT-cell activation |
| spellingShingle | Yuqi Zhu Zhengtao Jiang Lin Liu Xinyi Yang Min Li Yipeng Cheng Jianqing Xu Chunhua Yin Huanzhang Zhu Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation International Journal of Molecular Sciences Scopoletin HIV-1 latency reactivation NF-κB T-cell activation |
| title | Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation |
| title_full | Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation |
| title_fullStr | Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation |
| title_full_unstemmed | Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation |
| title_short | Scopoletin Reactivates Latent HIV-1 by Inducing NF-κB Expression without Global T Cell Activation |
| title_sort | scopoletin reactivates latent hiv 1 by inducing nf κb expression without global t cell activation |
| topic | Scopoletin HIV-1 latency reactivation NF-κB T-cell activation |
| url | https://www.mdpi.com/1422-0067/24/16/12649 |
| work_keys_str_mv | AT yuqizhu scopoletinreactivateslatenthiv1byinducingnfkbexpressionwithoutglobaltcellactivation AT zhengtaojiang scopoletinreactivateslatenthiv1byinducingnfkbexpressionwithoutglobaltcellactivation AT linliu scopoletinreactivateslatenthiv1byinducingnfkbexpressionwithoutglobaltcellactivation AT xinyiyang scopoletinreactivateslatenthiv1byinducingnfkbexpressionwithoutglobaltcellactivation AT minli scopoletinreactivateslatenthiv1byinducingnfkbexpressionwithoutglobaltcellactivation AT yipengcheng scopoletinreactivateslatenthiv1byinducingnfkbexpressionwithoutglobaltcellactivation AT jianqingxu scopoletinreactivateslatenthiv1byinducingnfkbexpressionwithoutglobaltcellactivation AT chunhuayin scopoletinreactivateslatenthiv1byinducingnfkbexpressionwithoutglobaltcellactivation AT huanzhangzhu scopoletinreactivateslatenthiv1byinducingnfkbexpressionwithoutglobaltcellactivation |