The cholesterol metabolite 25-hydroxycholesterol suppresses porcine deltacoronavirus via lipophagy inhibition and mTORC1 modulation
Abstract 25-Hydroxycholesterol (25HC) is a hydroxylated cholesterol with multiple antiviral activities, however, little is known about the mechanisms by which 25HC correlates antiviral ability with lipid droplet (LD) dynamic balance to ensure cholesterol homeostasis. In the present study, 25HC was a...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Veterinary Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13567-025-01452-9 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571435363598336 |
|---|---|
| author | Jia-lu Zhang Xue-fei Wang Jia-lin Li Cong Duan Jiu-feng Wang |
| author_facet | Jia-lu Zhang Xue-fei Wang Jia-lin Li Cong Duan Jiu-feng Wang |
| author_sort | Jia-lu Zhang |
| collection | DOAJ |
| description | Abstract 25-Hydroxycholesterol (25HC) is a hydroxylated cholesterol with multiple antiviral activities, however, little is known about the mechanisms by which 25HC correlates antiviral ability with lipid droplet (LD) dynamic balance to ensure cholesterol homeostasis. In the present study, 25HC was applied to porcine deltacoronavirus (PDCoV)-infected LLC-PK1 (Lilly Laboratories Culture-Porcine Kidney 1) cells and piglets to explore its antiviral capacity and underlying mechanism. The results revealed that 25HC decreased free cholesterol (FC) levels but increased triglyceride (TG) levels in PDCoV-infected cells and piglets. The accumulation of LDs induced by oleic acid (OA) impedes PDCoV replication. In addition, 25HC administration increases LD accumulation and declines protein expression associated with lipophagy and lysosomes to facilitate LD accumulation. Moreover, 25HC inhibited TFEB (transcription factor-EB) expression, blocked its translocation into the nucleus and reversed Mechanistic Target of Rapamycin Complex 1 (mTORC1) activity, which in turn hindered lipophagy and PDCoV replication. Additionally, 25HC treatment ameliorated the clinical symptoms and intestinal injury of PDCoV-infected piglets. These findings reveal the beneficial effect of lipophagy on PDCoV infection and uncover the antiviral mechanism of 25HC, by which lipophagy and mTOR activity are tightly controlled by 25HC. Graphical Abstract |
| format | Article |
| id | doaj-art-395952edf89549a88e31f6bba7c4cdcf |
| institution | Kabale University |
| issn | 1297-9716 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj-art-395952edf89549a88e31f6bba7c4cdcf2025-02-02T12:37:03ZengBMCVeterinary Research1297-97162025-01-0156111710.1186/s13567-025-01452-9The cholesterol metabolite 25-hydroxycholesterol suppresses porcine deltacoronavirus via lipophagy inhibition and mTORC1 modulationJia-lu Zhang0Xue-fei Wang1Jia-lin Li2Cong Duan3Jiu-feng Wang4National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural UniversityNational Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural UniversityChina Institute of Veterinary Drug ControlNational Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural UniversityAbstract 25-Hydroxycholesterol (25HC) is a hydroxylated cholesterol with multiple antiviral activities, however, little is known about the mechanisms by which 25HC correlates antiviral ability with lipid droplet (LD) dynamic balance to ensure cholesterol homeostasis. In the present study, 25HC was applied to porcine deltacoronavirus (PDCoV)-infected LLC-PK1 (Lilly Laboratories Culture-Porcine Kidney 1) cells and piglets to explore its antiviral capacity and underlying mechanism. The results revealed that 25HC decreased free cholesterol (FC) levels but increased triglyceride (TG) levels in PDCoV-infected cells and piglets. The accumulation of LDs induced by oleic acid (OA) impedes PDCoV replication. In addition, 25HC administration increases LD accumulation and declines protein expression associated with lipophagy and lysosomes to facilitate LD accumulation. Moreover, 25HC inhibited TFEB (transcription factor-EB) expression, blocked its translocation into the nucleus and reversed Mechanistic Target of Rapamycin Complex 1 (mTORC1) activity, which in turn hindered lipophagy and PDCoV replication. Additionally, 25HC treatment ameliorated the clinical symptoms and intestinal injury of PDCoV-infected piglets. These findings reveal the beneficial effect of lipophagy on PDCoV infection and uncover the antiviral mechanism of 25HC, by which lipophagy and mTOR activity are tightly controlled by 25HC. Graphical Abstracthttps://doi.org/10.1186/s13567-025-01452-9Porcine coronavirus25-Hydroxycholesterollipophagytranscription factor EBpiglets |
| spellingShingle | Jia-lu Zhang Xue-fei Wang Jia-lin Li Cong Duan Jiu-feng Wang The cholesterol metabolite 25-hydroxycholesterol suppresses porcine deltacoronavirus via lipophagy inhibition and mTORC1 modulation Veterinary Research Porcine coronavirus 25-Hydroxycholesterol lipophagy transcription factor EB piglets |
| title | The cholesterol metabolite 25-hydroxycholesterol suppresses porcine deltacoronavirus via lipophagy inhibition and mTORC1 modulation |
| title_full | The cholesterol metabolite 25-hydroxycholesterol suppresses porcine deltacoronavirus via lipophagy inhibition and mTORC1 modulation |
| title_fullStr | The cholesterol metabolite 25-hydroxycholesterol suppresses porcine deltacoronavirus via lipophagy inhibition and mTORC1 modulation |
| title_full_unstemmed | The cholesterol metabolite 25-hydroxycholesterol suppresses porcine deltacoronavirus via lipophagy inhibition and mTORC1 modulation |
| title_short | The cholesterol metabolite 25-hydroxycholesterol suppresses porcine deltacoronavirus via lipophagy inhibition and mTORC1 modulation |
| title_sort | cholesterol metabolite 25 hydroxycholesterol suppresses porcine deltacoronavirus via lipophagy inhibition and mtorc1 modulation |
| topic | Porcine coronavirus 25-Hydroxycholesterol lipophagy transcription factor EB piglets |
| url | https://doi.org/10.1186/s13567-025-01452-9 |
| work_keys_str_mv | AT jialuzhang thecholesterolmetabolite25hydroxycholesterolsuppressesporcinedeltacoronavirusvialipophagyinhibitionandmtorc1modulation AT xuefeiwang thecholesterolmetabolite25hydroxycholesterolsuppressesporcinedeltacoronavirusvialipophagyinhibitionandmtorc1modulation AT jialinli thecholesterolmetabolite25hydroxycholesterolsuppressesporcinedeltacoronavirusvialipophagyinhibitionandmtorc1modulation AT congduan thecholesterolmetabolite25hydroxycholesterolsuppressesporcinedeltacoronavirusvialipophagyinhibitionandmtorc1modulation AT jiufengwang thecholesterolmetabolite25hydroxycholesterolsuppressesporcinedeltacoronavirusvialipophagyinhibitionandmtorc1modulation AT jialuzhang cholesterolmetabolite25hydroxycholesterolsuppressesporcinedeltacoronavirusvialipophagyinhibitionandmtorc1modulation AT xuefeiwang cholesterolmetabolite25hydroxycholesterolsuppressesporcinedeltacoronavirusvialipophagyinhibitionandmtorc1modulation AT jialinli cholesterolmetabolite25hydroxycholesterolsuppressesporcinedeltacoronavirusvialipophagyinhibitionandmtorc1modulation AT congduan cholesterolmetabolite25hydroxycholesterolsuppressesporcinedeltacoronavirusvialipophagyinhibitionandmtorc1modulation AT jiufengwang cholesterolmetabolite25hydroxycholesterolsuppressesporcinedeltacoronavirusvialipophagyinhibitionandmtorc1modulation |