Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation
Enterovirus 71 (EV71) infection causes hand, foot, and mouth disease (HFMD), and even fatal neurological complications. However, the mechanisms underlying EV71 neurological pathogeneses are largely unknown. This study reveals a distinct mechanism by which EV71 induces apoptosis and autophagy in neur...
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Taylor & Francis Group
2020
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oai:doaj.org-article:54c40c775ee84d8db9f803900b8519912021-11-17T14:21:58ZEnterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation2150-55942150-560810.1080/21505594.2020.1766790https://doaj.org/article/54c40c775ee84d8db9f803900b8519912020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1766790https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Enterovirus 71 (EV71) infection causes hand, foot, and mouth disease (HFMD), and even fatal neurological complications. However, the mechanisms underlying EV71 neurological pathogeneses are largely unknown. This study reveals a distinct mechanism by which EV71 induces apoptosis and autophagy in neural cells. EV71 non-structure protein 3D (also known as RNA-dependent RNA polymerase, RdRp) interacts with the peroxisomal protein acyl-CoA oxidase 1 (ACOX1), and contributes to ACOX1 downregulation. Further studies demonstrate that EV71 reduces peroxisome numbers. Additionally, knockdown of ACOX1 or peroxin 19 (PEX19) induces apoptosis and autophagy in neural cells including human neuroblastoma (SK-N-SH) cells and human astrocytoma (U251) cells, and EV71 infection induces neural cell death through attenuating ACOX1 production. Moreover, EV71 infection and ACOX1 knockdown facilitate reactive oxygen species (ROS) production and attenuate the cytoprotective protein deglycase (DJ-1)/Nuclear factor erythroid 2-related factor 2 (NRF2)/Heme oxygenase 1 (HO-1) pathway (DJ-1/NRF2/HO-1), which collectively result in ROS accumulation in neural cells. In conclusion, EV71 downregulates ACOX1 protein expression, reduces peroxisome numbers, enhances ROS generation, and attenuates the DJ-1/NRF2/HO-1 pathway, thereby inducing apoptosis and autophagy in neural cells. These findings provide new insights into the mechanism underlying EV71-induced neural pathogenesis, and suggest potential treatments for EV71-associated diseases.Lei YouJunbo ChenWeiyong LiuQi XiangZhen LuoWenbiao WangWei XuKailang WuQi ZhangYingle LiuJianguo WuTaylor & Francis Grouparticlehand foot and mouth disease (hfmd)enterovirus 71 (ev71)neurological pathogenesisperoxisomeacyl-coa oxidase 1 (acox1)reactive oxygen species (ros)Infectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 537-553 (2020) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
hand foot and mouth disease (hfmd) enterovirus 71 (ev71) neurological pathogenesis peroxisome acyl-coa oxidase 1 (acox1) reactive oxygen species (ros) Infectious and parasitic diseases RC109-216 |
| spellingShingle |
hand foot and mouth disease (hfmd) enterovirus 71 (ev71) neurological pathogenesis peroxisome acyl-coa oxidase 1 (acox1) reactive oxygen species (ros) Infectious and parasitic diseases RC109-216 Lei You Junbo Chen Weiyong Liu Qi Xiang Zhen Luo Wenbiao Wang Wei Xu Kailang Wu Qi Zhang Yingle Liu Jianguo Wu Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation |
| description |
Enterovirus 71 (EV71) infection causes hand, foot, and mouth disease (HFMD), and even fatal neurological complications. However, the mechanisms underlying EV71 neurological pathogeneses are largely unknown. This study reveals a distinct mechanism by which EV71 induces apoptosis and autophagy in neural cells. EV71 non-structure protein 3D (also known as RNA-dependent RNA polymerase, RdRp) interacts with the peroxisomal protein acyl-CoA oxidase 1 (ACOX1), and contributes to ACOX1 downregulation. Further studies demonstrate that EV71 reduces peroxisome numbers. Additionally, knockdown of ACOX1 or peroxin 19 (PEX19) induces apoptosis and autophagy in neural cells including human neuroblastoma (SK-N-SH) cells and human astrocytoma (U251) cells, and EV71 infection induces neural cell death through attenuating ACOX1 production. Moreover, EV71 infection and ACOX1 knockdown facilitate reactive oxygen species (ROS) production and attenuate the cytoprotective protein deglycase (DJ-1)/Nuclear factor erythroid 2-related factor 2 (NRF2)/Heme oxygenase 1 (HO-1) pathway (DJ-1/NRF2/HO-1), which collectively result in ROS accumulation in neural cells. In conclusion, EV71 downregulates ACOX1 protein expression, reduces peroxisome numbers, enhances ROS generation, and attenuates the DJ-1/NRF2/HO-1 pathway, thereby inducing apoptosis and autophagy in neural cells. These findings provide new insights into the mechanism underlying EV71-induced neural pathogenesis, and suggest potential treatments for EV71-associated diseases. |
| format |
article |
| author |
Lei You Junbo Chen Weiyong Liu Qi Xiang Zhen Luo Wenbiao Wang Wei Xu Kailang Wu Qi Zhang Yingle Liu Jianguo Wu |
| author_facet |
Lei You Junbo Chen Weiyong Liu Qi Xiang Zhen Luo Wenbiao Wang Wei Xu Kailang Wu Qi Zhang Yingle Liu Jianguo Wu |
| author_sort |
Lei You |
| title |
Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation |
| title_short |
Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation |
| title_full |
Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation |
| title_fullStr |
Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation |
| title_full_unstemmed |
Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation |
| title_sort |
enterovirus 71 induces neural cell apoptosis and autophagy through promoting acox1 downregulation and ros generation |
| publisher |
Taylor & Francis Group |
| publishDate |
2020 |
| url |
https://doaj.org/article/54c40c775ee84d8db9f803900b851991 |
| work_keys_str_mv |
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| _version_ |
1718425480635351040 |