Wogonin inhibits latent HIV-1 reactivation by downregulating histone crotonylation

Zhang，Haitao1,2; Cai，Jinfeng3; Li，Chunna1; Deng，Lisi1; Zhu，Hongqiong1; Huang，Ting3; Zhao，Jiacong3; Zhou，Jiasheng3; Deng，Kai3; Hong，Zhongsi1; Xia，Jinyu1

2023-07-25

10.1016/j.phymed.2023.154855

Phytomedicine   影响因子和分区

0944-7113

1618-095X

Background: Wogonin, a flavone isolated from Scutellaria baicalensis Georgi, is a commonly used phytochemical with anti-inflammatory and antitumor properties. However, the antiviral activity of wogonin against human immunodeficiency virus type 1 (HIV-1) has not been reported. Purpose: The current study aimed to explore whether wogonin can suppress latent HIV-1 reactivation and the mechanism of wogonin in inhibiting proviral HIV-1 transcription. Methods: We assessed the effects of wogonin on HIV-1 reactivation using flow cytometry, cytotoxicity assay, quantitative PCR (qPCR), viral quality assurance (VQA), and western blot analysis. Results: Wogonin, a flavone isolated from S. baicalensis, significantly inhibited the reactivation of latent HIV-1 in cellular models and in primary CD4+ T cells from antiretroviral therapy (ART)-suppressed individuals ex vivo. Wogonin exhibited low cytotoxicity and long-lasting inhibition of HIV-1 transcription. Triptolide is a latency-promoting agent (LPA) that inhibits HIV-1 transcription and replication; wogonin had a stronger ability to inhibit HIV-1 latent reactivation than triptolide. Mechanistically, wogonin inhibited the reactivation of latent HIV-1 by inhibiting the expression of p300, a histone acetyltransferase, and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. Conclusion: Our study found that wogonin is a novel LPA that can inhibit HIV-1 transcription by HIV-1 epigenetic silencing, which could bear promising significance for future applications of HIV-1 functional cure.

Crotonylation Latency-promoting agents Latent hiv-1 Wogonin

SCI

英语

其他

Rottapharm|Madaus[2020B111105001];

Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine

Plant Sciences ; Chemistry, Medicinal ; Integrative & Complementary Medicine ; Pharmacology & Pharmacy

WOS:001001250100001

ELSEVIER GMBH

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85158870435

Scopus

1.Department of Infectious Diseases,Fifth Affiliated Hospital,Sun Yat-sen University,Zhuhai,China
2.Ward 1 of infection Department,Shenzhen Third People's Hospital,The Second Hospital Affiliated with the School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,China
3.Institute of Human Virology,Key Laboratory of Tropical Disease Control of Ministry of Education,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,China

Zhang，Haitao,Cai，Jinfeng,Li，Chunna,et al. Wogonin inhibits latent HIV-1 reactivation by downregulating histone crotonylation[J]. Phytomedicine,2023,116.

Zhang，Haitao.,Cai，Jinfeng.,Li，Chunna.,Deng，Lisi.,Zhu，Hongqiong.,...&Xia，Jinyu.(2023).Wogonin inhibits latent HIV-1 reactivation by downregulating histone crotonylation.Phytomedicine,116.

Zhang，Haitao,et al."Wogonin inhibits latent HIV-1 reactivation by downregulating histone crotonylation".Phytomedicine 116(2023).