PRMT3 reverses HIV-1 latency by increasing chromatin accessibility to form a TEAD4-P-TEFb-containing transcriptional hub

Xinyu Wang, Yuhua Xue, Lin Li, Jinwen Song, Lei Jia, Xu Li, Miao Fan, Lu Lu, Wen Su, Jingwan Han, Dandan Lin, Rongdiao Liu, Xiang Gao, Yafei Guo, Zixun Xiang, Chunjing Chen, Linyu Wan, Huihui Chong, Yuxian He, Fusheng Wang, Kaihu Yao (), Qiang Zhou () and Dan Yu ()
Additional contact information
Xinyu Wang: National Center for Children’s Health
Yuhua Xue: Xiamen University
Lin Li: Academy of Military Medical Sciences
Jinwen Song: National Clinical Research Center for Infectious Diseases
Lei Jia: Academy of Military Medical Sciences
Xu Li: The First Hospital of Hohhot
Miao Fan: National Center for Children’s Health
Lu Lu: National Center for Children’s Health
Wen Su: National Center for Children’s Health
Jingwan Han: Academy of Military Medical Sciences
Dandan Lin: Academy of Military Medical Sciences
Rongdiao Liu: Xiamen University
Xiang Gao: Xiamen University
Yafei Guo: Xiamen University
Zixun Xiang: Xiamen University
Chunjing Chen: Xiamen University
Linyu Wan: University of Science and Technology of China
Huihui Chong: Chinese Academy of Medical Sciences and Peking Union Medical College
Yuxian He: Chinese Academy of Medical Sciences and Peking Union Medical College
Fusheng Wang: National Clinical Research Center for Infectious Diseases
Kaihu Yao: National Center for Children’s Health
Qiang Zhou: The University of Hong Kong
Dan Yu: National Center for Children’s Health

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Latent HIV-1 presents a formidable challenge for viral eradication. HIV-1 transcription and latency reversal require interactions between the viral promoter and host proteins. Here, we perform the dCas9-targeted locus-specific protein analysis and discover the interaction of human arginine methyltransferase 3 (PRMT3) with the HIV-1 promoter. This interaction reverses latency in cell line models and primary cells from latently infected persons by increasing the levels of H4R3Me2a and transcription factor P-TEFb at the viral promoter. PRMT3 is found to promote chromatin accessibility and transcription of HIV-1 and a small subset of host genes in regions harboring the classical recognition motif for another transcription factor TEAD4. This motif attracts TEAD4 and PRMT3 to the viral promoter to synergistically activate transcription. Physical interactions among PRMT3, P-TEFb, and TEAD4 exist, which may help form a transcriptional hub at the viral promoter. Our study reveals the potential of targeting these hub proteins to eradicate latent HIV-1.

Date: 2025
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DOI: 10.1038/s41467-025-59578-5

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