Effect of Xanthium Strumarium on HIV-1 5′-LTR Transcriptional Activity and Viral Reactivation in Latently Infected Cells
Chinese herbal medicines (CHMs) are widely used in Asian countries. They show multiple pharmacological activities, including antiviral activities. The 5′-long terminal repeat (LTR) region of HIV-1, required for viral transcription, is a potential drug target for HIV-1 reactivation and intrinsic cell...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.720821/full |
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| author | Chao-Jung Chen Chao-Jung Chen Mu-Lin Chiu Chien-Hui Hung Chien-Hui Hung Wen-Miin Liang Mao-Wang Ho Mao-Wang Ho Ting-Hsu Lin Xiang Liu Hsinyi Tsang Chiu-Chu Liao Shao-Mei Huang Yi-Fang Wu Yang-Chang Wu Yang-Chang Wu Yang-Chang Wu Te-Mao Li Fuu-Jen Tsai Fuu-Jen Tsai Fuu-Jen Tsai Ying-Ju Lin Ying-Ju Lin |
| author_facet | Chao-Jung Chen Chao-Jung Chen Mu-Lin Chiu Chien-Hui Hung Chien-Hui Hung Wen-Miin Liang Mao-Wang Ho Mao-Wang Ho Ting-Hsu Lin Xiang Liu Hsinyi Tsang Chiu-Chu Liao Shao-Mei Huang Yi-Fang Wu Yang-Chang Wu Yang-Chang Wu Yang-Chang Wu Te-Mao Li Fuu-Jen Tsai Fuu-Jen Tsai Fuu-Jen Tsai Ying-Ju Lin Ying-Ju Lin |
| author_sort | Chao-Jung Chen |
| collection | DOAJ |
| description | Chinese herbal medicines (CHMs) are widely used in Asian countries. They show multiple pharmacological activities, including antiviral activities. The 5′-long terminal repeat (LTR) region of HIV-1, required for viral transcription, is a potential drug target for HIV-1 reactivation and intrinsic cell death induction of infected or latently infected cells. Modulation of HIV-1 reactivation requires interactions between host cell proteins and viral 5′-LTR elements. By evaluation of two CHMs- Xanthium strumarium and Pueraria montana, we found that 1) X. strumarium reactivated HIV-1 latently infected cells in J-Lat 8.4, J-Lat 9.2, U1, and ACH-2 cells in vitro; 2) 27 nuclear regulatory proteins were associated with HIV-1 5′-LTR using deoxyribonucleic acid affinity pull-down and LC-MS/MS analyses; and 3) among them, silencing of XRCC6 reactivated HIV-1 5′-LTR transcriptional activity. We found that X. strumarium inhibits the 5′-LTR associated XRCC6 nuclear regulatory proteins, increases its viral 5′-LTR promoter transcriptional activity, and reactivates HIV-1 latently infected cells in vitro. These findings may contribute to understanding the 5′-LTR activity and the host cell nuclear regulatory protein machinery for reactivating HIV-1 and for future investigations to eradicate and cure HIV-1 infection. |
| first_indexed | 2024-12-20T15:18:13Z |
| format | Article |
| id | doaj.art-3525a37fa40f49ddb84370718f0417c4 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T15:18:13Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-3525a37fa40f49ddb84370718f0417c42022-12-21T19:36:07ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-08-011210.3389/fphar.2021.720821720821Effect of Xanthium Strumarium on HIV-1 5′-LTR Transcriptional Activity and Viral Reactivation in Latently Infected CellsChao-Jung Chen0Chao-Jung Chen1Mu-Lin Chiu2Chien-Hui Hung3Chien-Hui Hung4Wen-Miin Liang5Mao-Wang Ho6Mao-Wang Ho7Ting-Hsu Lin8Xiang Liu9Hsinyi Tsang10Chiu-Chu Liao11Shao-Mei Huang12Yi-Fang Wu13Yang-Chang Wu14Yang-Chang Wu15Yang-Chang Wu16Te-Mao Li17Fuu-Jen Tsai18Fuu-Jen Tsai19Fuu-Jen Tsai20Ying-Ju Lin21Ying-Ju Lin22Genetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, TaiwanGraduate Institute of Integrated Medicine, China Medical University, Taichung, TaiwanSchool of Chinese Medicine, China Medical University, Taichung, TaiwanGraduate Institute of Clinical Medical Sciences, Chang-Gung University, Taoyuan, TaiwanDivision of Infectious Diseases, Chang Gung Memorial Hospital Chiayi Branch, Chiayi, TaiwanDepartment of Health Services Administration, China Medical University, Taichung, TaiwanSection of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, Taichung, TaiwanDepartment of Internal Medicine, School of Medicine, China Medical University, Taichung, TaiwanGenetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, TaiwanNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesGenetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, TaiwanGenetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, TaiwanGenetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, TaiwanGraduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan0Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan1Department of Biotechnology and Bioinformatics, Asia University, Taichung, TaiwanSchool of Chinese Medicine, China Medical University, Taichung, TaiwanGenetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, TaiwanSchool of Chinese Medicine, China Medical University, Taichung, Taiwan1Department of Biotechnology and Bioinformatics, Asia University, Taichung, TaiwanGenetic Center, Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, TaiwanSchool of Chinese Medicine, China Medical University, Taichung, TaiwanChinese herbal medicines (CHMs) are widely used in Asian countries. They show multiple pharmacological activities, including antiviral activities. The 5′-long terminal repeat (LTR) region of HIV-1, required for viral transcription, is a potential drug target for HIV-1 reactivation and intrinsic cell death induction of infected or latently infected cells. Modulation of HIV-1 reactivation requires interactions between host cell proteins and viral 5′-LTR elements. By evaluation of two CHMs- Xanthium strumarium and Pueraria montana, we found that 1) X. strumarium reactivated HIV-1 latently infected cells in J-Lat 8.4, J-Lat 9.2, U1, and ACH-2 cells in vitro; 2) 27 nuclear regulatory proteins were associated with HIV-1 5′-LTR using deoxyribonucleic acid affinity pull-down and LC-MS/MS analyses; and 3) among them, silencing of XRCC6 reactivated HIV-1 5′-LTR transcriptional activity. We found that X. strumarium inhibits the 5′-LTR associated XRCC6 nuclear regulatory proteins, increases its viral 5′-LTR promoter transcriptional activity, and reactivates HIV-1 latently infected cells in vitro. These findings may contribute to understanding the 5′-LTR activity and the host cell nuclear regulatory protein machinery for reactivating HIV-1 and for future investigations to eradicate and cure HIV-1 infection.https://www.frontiersin.org/articles/10.3389/fphar.2021.720821/fullhuman immunodeficiency virus type 1 latencyChinese herbal medicineX. strumarium5′-long terminal repeatnuclear regulatory proteins |
| spellingShingle | Chao-Jung Chen Chao-Jung Chen Mu-Lin Chiu Chien-Hui Hung Chien-Hui Hung Wen-Miin Liang Mao-Wang Ho Mao-Wang Ho Ting-Hsu Lin Xiang Liu Hsinyi Tsang Chiu-Chu Liao Shao-Mei Huang Yi-Fang Wu Yang-Chang Wu Yang-Chang Wu Yang-Chang Wu Te-Mao Li Fuu-Jen Tsai Fuu-Jen Tsai Fuu-Jen Tsai Ying-Ju Lin Ying-Ju Lin Effect of Xanthium Strumarium on HIV-1 5′-LTR Transcriptional Activity and Viral Reactivation in Latently Infected Cells Frontiers in Pharmacology human immunodeficiency virus type 1 latency Chinese herbal medicine X. strumarium 5′-long terminal repeat nuclear regulatory proteins |
| title | Effect of Xanthium Strumarium on HIV-1 5′-LTR Transcriptional Activity and Viral Reactivation in Latently Infected Cells |
| title_full | Effect of Xanthium Strumarium on HIV-1 5′-LTR Transcriptional Activity and Viral Reactivation in Latently Infected Cells |
| title_fullStr | Effect of Xanthium Strumarium on HIV-1 5′-LTR Transcriptional Activity and Viral Reactivation in Latently Infected Cells |
| title_full_unstemmed | Effect of Xanthium Strumarium on HIV-1 5′-LTR Transcriptional Activity and Viral Reactivation in Latently Infected Cells |
| title_short | Effect of Xanthium Strumarium on HIV-1 5′-LTR Transcriptional Activity and Viral Reactivation in Latently Infected Cells |
| title_sort | effect of xanthium strumarium on hiv 1 5 ltr transcriptional activity and viral reactivation in latently infected cells |
| topic | human immunodeficiency virus type 1 latency Chinese herbal medicine X. strumarium 5′-long terminal repeat nuclear regulatory proteins |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.720821/full |
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