Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication
Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus (PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory respon...
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
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| Series: | Journal of Integrative Agriculture |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095311923003520 |
| _version_ | 1797261834745544704 |
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| author | Qi Gao Yongzhi Feng Ting Gong Dongdong Wu Xiaoyu Zheng Yizhuo Luo Yunlong Yang Zebu Song Lang Gong Guihong Zhang |
| author_facet | Qi Gao Yongzhi Feng Ting Gong Dongdong Wu Xiaoyu Zheng Yizhuo Luo Yunlong Yang Zebu Song Lang Gong Guihong Zhang |
| author_sort | Qi Gao |
| collection | DOAJ |
| description | Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus (PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets (LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections. |
| first_indexed | 2024-04-24T23:47:31Z |
| format | Article |
| id | doaj.art-4c9da81dbe6b43968ff412bb7a8ff611 |
| institution | Directory Open Access Journal |
| issn | 2095-3119 |
| language | English |
| last_indexed | 2024-04-24T23:47:31Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Integrative Agriculture |
| spelling | doaj.art-4c9da81dbe6b43968ff412bb7a8ff6112024-03-15T04:43:11ZengElsevierJournal of Integrative Agriculture2095-31192024-03-012339881005Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replicationQi Gao0Yongzhi Feng1Ting Gong2Dongdong Wu3Xiaoyu Zheng4Yizhuo Luo5Yunlong Yang6Zebu Song7Lang Gong8Guihong Zhang9Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming 525000, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou 510000, ChinaGuangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou 510000, ChinaGuangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, ChinaGuangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, ChinaGuangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou 510000, ChinaGuangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming 525000, ChinaGuangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming 525000, ChinaGuangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, ChinaGuangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming 525000, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China; Correspondence Lang GongGuangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China; Correspondence Guihong ZhangCoronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus (PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets (LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.http://www.sciencedirect.com/science/article/pii/S2095311923003520porcine enteric alphacoronavirusNF-κB inflammatory pathwaylipid dropletmetformin hydrochloride |
| spellingShingle | Qi Gao Yongzhi Feng Ting Gong Dongdong Wu Xiaoyu Zheng Yizhuo Luo Yunlong Yang Zebu Song Lang Gong Guihong Zhang Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication Journal of Integrative Agriculture porcine enteric alphacoronavirus NF-κB inflammatory pathway lipid droplet metformin hydrochloride |
| title | Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication |
| title_full | Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication |
| title_fullStr | Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication |
| title_full_unstemmed | Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication |
| title_short | Porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication |
| title_sort | porcine enteric alphacoronavirus infection increases lipid droplet accumulation to facilitate the virus replication |
| topic | porcine enteric alphacoronavirus NF-κB inflammatory pathway lipid droplet metformin hydrochloride |
| url | http://www.sciencedirect.com/science/article/pii/S2095311923003520 |
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