AUTHOR=Chen Chao-Jung , Chiu Mu-Lin , Hung Chien-Hui , Liang Wen-Miin , Ho Mao-Wang , Lin Ting-Hsu , Liu Xiang , Tsang Hsinyi , Liao Chiu-Chu , Huang Shao-Mei , Wu Yi-Fang , Wu Yang-Chang , Li Te-Mao , Tsai Fuu-Jen , Lin Ying-Ju TITLE=Effect of Xanthium Strumarium on HIV-1 5′-LTR Transcriptional Activity and Viral Reactivation in Latently Infected Cells JOURNAL=Frontiers in Pharmacology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.720821 DOI=10.3389/fphar.2021.720821 ISSN=1663-9812 ABSTRACT=

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.