4.7 Article

Phillygenin activates PKR/eIF2a pathway and induces stress granule to exert anti-avian infectious bronchitis virus

Journal

INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 108, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.intimp.2022.108764

Keywords

Avian infectious bronchitis virus; Phillygenin; Stress granule; Antiviral activity; PKR/eIF2 alpha pathway

Funding

  1. Agricultural Sciences and Technology Innovation Program [CAAS-ZDXT2018008, CAAS-LMY-02]
  2. National key research and development program of China [2017YFE0114400]
  3. National Natural Science Foundation of China [31602101]

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Avian infectious bronchitis virus (IBV) is a cause of severe production losses in the poultry industry worldwide. This study found that phillygenin, a compound found in Forsythiae Fructus, can inhibit IBV replication by interfering with multiple stages of the virus life cycle. It activates the antiviral response in cells and shows potential as a novel drug for IBV prevention.
The prevalence of avian infectious bronchitis virus (IBV) is still one of causes inducing severe losses of production in the poultry industry worldwide. Vaccination does not completely prevent IBV infection and spread due to immune failure and viral mutations. Forsythiae Fructus and its compounds have been widely used in a lot of prescriptions of the traditional Chinese medicine for a long history, and it is well-known as safety and efficiency in heat-clearing and detoxifying. This study aims to investigate the anti-IBV activity and mechanism of phillygenin. The results showed that phillygenin inhibited IBV replication by disturbing multiple stages of the virus life cycle, including viral adsorption, invasion, internalization, and release in Vero cells. After being treated with 100, 125 and 150 mu g/mL phillygenin, the expression of G3BP1 was significantly increased and the phosphorylation of PKR/eIF2 alpha was activated, which increased stress granule, thereby triggering the antiviral response in Vero cells. The anti-virus activity of PHI was decreased when G3BP1 was interfered by si-RNA, and G3BP1 was down-regulated when PKR/eIF2 alpha was interfered by si-RNA. In conclusion, our findings indicate that phillygenin activates PKR/eIF2 alpha pathway and induces stress granule formation to exert anti-IBV, which holds promise to develop into a novel anti-IBV drug. Further study in vivo is needed to explore phillygenin as a potential and effective drug to prevent IB in poultry.& nbsp;

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