The Chinese herbal prescription JZ-1 promotes extracellular vesicle production and protects against herpes simplex virus type 2 infection in vitro

Wenjia Wang; Ximing Jin; Qingqing Shao; Tong Liu; Tianli Liu; Xinwei Zhao; Lijun Xu; Wen Gao; Liu Hu; Zhuo Chen

Heliyon (Mar 2024)

The Chinese herbal prescription JZ-1 promotes extracellular vesicle production and protects against herpes simplex virus type 2 infection in vitro

Wenjia Wang,
Ximing Jin,
Qingqing Shao,
Tong Liu,
Tianli Liu,
Xinwei Zhao,
Lijun Xu,
Wen Gao,
Liu Hu,
Zhuo Chen

Affiliations

Wenjia Wang: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Ximing Jin: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Qingqing Shao: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Tong Liu: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Tianli Liu: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Xinwei Zhao: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Lijun Xu: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Wen Gao: Health Management Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Liu Hu: Health Management Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Zhuo Chen: Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Corresponding author. Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Journal volume & issue: Vol. 10, no. 5
p. e27019

Abstract

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Objective: Genital herpes, primarily caused by HSV-2 infection, remains a widespread sexually transmitted ailment. Extracellular vesicles play a pivotal role in host-virus confrontation. Recent research underscores the influence of Chinese herbal prescriptions on extracellular vesicle production and composition. This study aims to probe the impact of JieZe-1 (JZ-1) on extracellular vesicle components, elucidating its mechanisms against HSV-2 infection via extracellular vesicles. Methods: The JZ-1's anti-HSV-2 effects were assessed using CCK-8 assay. Extracellular vesicles were precisely isolated utilizing ultracentrifugation and subsequently characterized through TEM, NTA, and Western Blot analyses. The anti-HSV-2 activity of extracellular vesicles was gauged using CCK-8, Western Blot, and immunofluorescence. Additionally, high-throughput sequencing was employed to detect miRNAs from extracellular vesicles, unraveling the potential antiviral mechanisms of JZ-1. Results: Antiviral efficacy of JZ-1 was shown in VK2/E6E7, HeLa, and Vero cells. The samples extracted from cell supernatant by ultracentrifugation were identified as extracellular vesicles. In VK2/E6E7 cells, extracellular vesicles from JZ-1 group enhanced cell survival rates and diminished the expression of intracellular viral protein gD, contrasting with the inert effect of control group vesicles. Extracellular vesicles from JZ-1 treated Vero cells demonstrated a weaker yet discernible anti-HSV-2 effect. Conversely, extracellular vesicles of HeLa cells exhibited no anti-HSV-2 effect from either group. High-throughput sequencing of VK2/E6E7 cell extracellular vesicles unveiled significant upregulation of miRNA-101, miRNA-29a, miRNA-29b, miRNA-29c, and miRNA-637 in JZ-1 group vesicles. KEGG pathway analysis suggested that these miRNAs may inhibit PI3K/AKT/mTOR signaling pathway and induce autophagy of host cells to protect against HSV-2. Western blot confirmed the induction of autophagy and inhibition of AKT/mTOR in VK2/E6E7 cells with JZ-1 group extracellular vesicles treatment. Conclusion: JZ-1 had an anti-HSV-2 efficacy. After JZ-1 stimulation, VK2/E6E7 cells secreted extracellular vesicles which protect host cells from HSV-2 infection. High-throughput sequencing showed that these extracellular vesicles contained a large number of miRNAs targeting PI3K/AKT/mTOR pathway. JZ-1 group extracellular vesicles could inhibit the activation of AKT/mTOR pathway and induce the host cells autophagy.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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