GCRV-II major outer capsid protein VP4 promotes cell apoptosis by VDAC2-mediated calcium pathway facilitation

被引：0

作者：

Zhao, Kaiwen ^{[1
]}

Zhang, Yansong ^{[1
]}

Yin, Zijia ^{[1
]}

Tan, Libo ^{[3
]}

Juario, Ming ^{[4
]}

Zhang, Hongying ^{[1
]}

Liu, Yulong ^{[1
]}

Xu, Pengxia ^{[1
]}

Zhang, Qin ^{[1
]}

Zhao, Guannan ^{[1
]}

Wang, Shanghong ^{[1
]}

Mao, Huiling ^{[1
]}

Xu, Xiaowen ^{[1
,2
]}

Hu, Chengyu ^{[1
]}

机构：

[1] Nanchang Univ, Sch Life Sci, Nanchang 330031, Peoples R China

[2] Nanchang Univ, Chongqing Res Inst, Chongqing 402660, Peoples R China

[3] Univ Alabama, Dept Human Nutr, Tuscaloosa, AL 35487 USA

[4] HCA Florida West Marion Hosp, Food & Nutr Dept, Ocala, FL 34474 USA

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES | 2025年 / 285卷

基金：

中国国家自然科学基金;

关键词：

GCRV; Major outer capsid protein VP4; VDAC2; Ca plus; Apoptosis; DEPENDENT ANION CHANNEL; GRASS CARP REOVIRUS; CORE; AQUAREOVIRUS; MITOCHONDRIA; RETICULUM; SEQUENCE; BINDING; VDAC;

D O I：

10.1016/j.ijbiomac.2024.138273

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Grass Carp Reovirus (GCRV) is widely concerned because of its widespread prevalence and high mortality to grass carp (Ctenopharyngodon idellus). Viral protein 4 (VP4) is an important major outer capsid protein of GCRV and is involved in the regulation of cell cycle and cycle of GCRV replication. However, the elaborate function of VP4 remains to be explicated. To understand its function, we screened the transcriptome of Ctenopharyngodon idellus kidney (CIK) cells transfected with VP4 and found that VP4 may be involved in regulation of ion trans- membrane transporter activity and calcium signaling pathway. It was observed through transmission electron microscopy and confocal microscopy. VP4 causes endoplasmic reticulum (ER) stress and leads to abnormal Calcium ions (Ca2+) concentration in cells. Also, VP4 promoted the loss of mitochondrial membrane potential, which allowed a large amount of Ca2+ to enter mitochondria and led to mitochondrial damage and apoptosis. In this transcriptome, we found that voltage-dependent anion channel 2 (VDAC2) was significantly upregulated. Moreover, the results also showed that the expression of C.idellus voltage-dependent anion channel 2 (CiVDAC2) and the degree of cell apoptosis were increased along with the increase of VP4 transfection. In contrast, knockdown of CiVDAC2 can reduce the concentration of Ca2+ and the occurrence of apoptosis caused by VP4 transfection. In conclusion, the results demonstrated that VP4 can induce cell apoptosis through VDAC2mediated calcium pathway facilitation. This study provides some insights for the prevention and treatment of GCRV infection in grass carp.

引用

页数：24

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