African Swine Fever Virus K205R Induces ER Stress and Consequently Activates Autophagy and the NF-κB Signaling Pathway
African swine fever virus (ASFV) is responsible for enormous economic losses in the global swine industry. The ASFV genome encodes approximate 160 proteins, most of whose functions remain largely unknown. In this study, we examined the roles of ASFV K205R in endoplasmic reticulum (ER) stress, autoph...
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MDPI AG
2022-02-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/2/394 |
| _version_ | 1797475964178923520 |
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| author | Qi Wang Luyu Zhou Jiang Wang Dan Su Dahua Li Yongkun Du Guoyu Yang Gaiping Zhang Beibei Chu |
| author_facet | Qi Wang Luyu Zhou Jiang Wang Dan Su Dahua Li Yongkun Du Guoyu Yang Gaiping Zhang Beibei Chu |
| author_sort | Qi Wang |
| collection | DOAJ |
| description | African swine fever virus (ASFV) is responsible for enormous economic losses in the global swine industry. The ASFV genome encodes approximate 160 proteins, most of whose functions remain largely unknown. In this study, we examined the roles of ASFV K205R in endoplasmic reticulum (ER) stress, autophagy, and inflammation. We observed that K205R was located in both the cytosolic and membrane fractions, and formed stress granules in cells. Furthermore, K205R triggered ER stress and activated the unfolded protein response through activating the transcription factor 6, ER to nucleus signaling 1, and eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3/PERK) signaling pathways. Moreover, K205R inhibited the serine/threonine kinase 1 and the mechanistic target of the rapamycin kinase signaling pathway, thereby activating unc-51 like autophagy activating kinase 1, and hence autophagy. In addition, K205R stimulated the translocation of P65 into the nucleus and the subsequent activation of the nuclear factor kappa B (NF-κB) signaling pathway. Inhibition of ER stress with a PERK inhibitor attenuated K205R-induced autophagy and NF-κB activation. Our data demonstrated a previously uncharacterized role of ASFV K205R in ER stress, autophagy, and the NF-κB signaling pathway. |
| first_indexed | 2024-03-09T20:51:16Z |
| format | Article |
| id | doaj.art-1b0f26733cca4ca5b30b3ea061e7dbb4 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T20:51:16Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-1b0f26733cca4ca5b30b3ea061e7dbb42023-11-23T22:32:11ZengMDPI AGViruses1999-49152022-02-0114239410.3390/v14020394African Swine Fever Virus K205R Induces ER Stress and Consequently Activates Autophagy and the NF-κB Signaling PathwayQi Wang0Luyu Zhou1Jiang Wang2Dan Su3Dahua Li4Yongkun Du5Guoyu Yang6Gaiping Zhang7Beibei Chu8College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaKey Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaCollege of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, ChinaAfrican swine fever virus (ASFV) is responsible for enormous economic losses in the global swine industry. The ASFV genome encodes approximate 160 proteins, most of whose functions remain largely unknown. In this study, we examined the roles of ASFV K205R in endoplasmic reticulum (ER) stress, autophagy, and inflammation. We observed that K205R was located in both the cytosolic and membrane fractions, and formed stress granules in cells. Furthermore, K205R triggered ER stress and activated the unfolded protein response through activating the transcription factor 6, ER to nucleus signaling 1, and eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3/PERK) signaling pathways. Moreover, K205R inhibited the serine/threonine kinase 1 and the mechanistic target of the rapamycin kinase signaling pathway, thereby activating unc-51 like autophagy activating kinase 1, and hence autophagy. In addition, K205R stimulated the translocation of P65 into the nucleus and the subsequent activation of the nuclear factor kappa B (NF-κB) signaling pathway. Inhibition of ER stress with a PERK inhibitor attenuated K205R-induced autophagy and NF-κB activation. Our data demonstrated a previously uncharacterized role of ASFV K205R in ER stress, autophagy, and the NF-κB signaling pathway.https://www.mdpi.com/1999-4915/14/2/394ASFV K205Rstress granulesER stressautophagyNF-κB |
| spellingShingle | Qi Wang Luyu Zhou Jiang Wang Dan Su Dahua Li Yongkun Du Guoyu Yang Gaiping Zhang Beibei Chu African Swine Fever Virus K205R Induces ER Stress and Consequently Activates Autophagy and the NF-κB Signaling Pathway Viruses ASFV K205R stress granules ER stress autophagy NF-κB |
| title | African Swine Fever Virus K205R Induces ER Stress and Consequently Activates Autophagy and the NF-κB Signaling Pathway |
| title_full | African Swine Fever Virus K205R Induces ER Stress and Consequently Activates Autophagy and the NF-κB Signaling Pathway |
| title_fullStr | African Swine Fever Virus K205R Induces ER Stress and Consequently Activates Autophagy and the NF-κB Signaling Pathway |
| title_full_unstemmed | African Swine Fever Virus K205R Induces ER Stress and Consequently Activates Autophagy and the NF-κB Signaling Pathway |
| title_short | African Swine Fever Virus K205R Induces ER Stress and Consequently Activates Autophagy and the NF-κB Signaling Pathway |
| title_sort | african swine fever virus k205r induces er stress and consequently activates autophagy and the nf κb signaling pathway |
| topic | ASFV K205R stress granules ER stress autophagy NF-κB |
| url | https://www.mdpi.com/1999-4915/14/2/394 |
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