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ALV-J inhibits autophagy through the GADD45 beta/MEKK4/P38MAPK signaling pathway and mediates apoptosis following autophagy

文献类型： 外文期刊

作者： Liao, Zhihong 1 ; Zhang, Xinheng 1 ; Song, Cailiang 1 ; Lin, Wencheng 1 ; Cheng, Yuzhen 1 ; Xie, Zi 1 ; Chen, Sheng 1 ; N 1 ;

作者机构： 1.South China Agr Univ, Coll Anim Sci, Lingnan Guangdong Lab Modern Agr, Guangzhou 510642, Peoples R China

2.South China Agr Univ, Coll Anim Sci, Guangdong Prov Key Lab Agroanim Genom & Mol Breed, Guangzhou 510642, Peoples R China

3.Key Lab Anim Hlth Aquaculture & Environm Control, Guangzhou 510642, Guangdong, Peoples R China

4.South China Collaborat Innovat Ctr Poultry Dis Co, Guangzhou 510642, Peoples R China

5.Guangdong Engn Res Ctr Vector Vaccine Anim Virus, Guangzhou 510642, Peoples R China

6.Jinan Univ, Coll Sci & Engn, Guangzhou 510632, Peoples R China

7.ARS, USDA, Avian Dis & Oncol Lab, E Lansing, MI 48823 USA

期刊名称：CELL DEATH & DISEASE （ 影响因子：8.469； 五年影响因子：8.713 ）

ISSN： 2041-4889

年卷期： 2020 年 11 卷 8 期

页码：

收录情况： SCI

摘要： Autophagy and apoptosis, which are important processes for host immunity, are commonly exploited by viruses to facilitate their survival. However, to the best of our knowledge, very few studies have researched the mechanisms of action of the autophagic and apoptotic signaling pathways following viral infection. Thus, the present study aimed to investigate the mechanisms of action of growth arrest and DNA-damage-inducible beta (GADD45 beta), an important resistance gene involved in the host resistance to ALV-J. Both ALV-J infection and the overexpression of GADD45 beta inhibited autophagy during the early stages, which prevented the autophagosomes from binding to the lysosomes and resulted in an incomplete autophagic flux. Notably, GADD45 beta was discovered to interact with MEKK4 in DF-1 cells. The genetic knockdown of GADD45 beta and MEKK4 using small interfering RNA-affected ALV-J infection, which suggested that ALV-J may promote the binding of GADD45 beta to MEKK4 to activate the p38MAPK signaling pathway, which subsequently inhibits autophagy. Furthermore, ALV-J was revealed to affect the autophagic pathway prior to affecting the apoptotic pathway. In conclusion, to the best of our knowledge, the present study was the first to investigate the combined effects of ALV-J infection on autophagy and apoptosis, and to suggest that ALV-J inhibits autophagy via the GADD45 beta/MEKK4/p38MAPK signaling pathway.

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