Fowl adenovirus serotype 4 enters leghorn male hepatocellular cells via the clathrin-mediated endocytosis pathway
Abstract Hepatitis-hydropericardium syndrome (HHS) induced by fowl adenovirus serotype-4 (FAdV-4) has caused large economic losses to the world poultry industry in recent years. HHS is characterized by pericardial effusion and hepatitis, manifesting as a swollen liver with focal necroses and petechi...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Veterinary Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13567-023-01155-z |
| _version_ | 1797863808130088960 |
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| author | Ting Wang Lizhen Wang Wei Li Xiaolan Hou Wenchi Chang Bo Wen Shuizhong Han Yan Chen Xuefeng Qi Jingyu Wang |
| author_facet | Ting Wang Lizhen Wang Wei Li Xiaolan Hou Wenchi Chang Bo Wen Shuizhong Han Yan Chen Xuefeng Qi Jingyu Wang |
| author_sort | Ting Wang |
| collection | DOAJ |
| description | Abstract Hepatitis-hydropericardium syndrome (HHS) induced by fowl adenovirus serotype-4 (FAdV-4) has caused large economic losses to the world poultry industry in recent years. HHS is characterized by pericardial effusion and hepatitis, manifesting as a swollen liver with focal necroses and petechial haemorrhage. However, the process of FAdV-4 entry into hepatic cells remains largely unknown. In this paper, we present a comprehensive study on the entry mechanism of FAdV-4 into leghorn male hepatocellular (LMH) cells. We first observed that FAdV-4 internalization was inhibited by chlorpromazine and clathrin heavy chain (CHC) knockdown, suggesting that FAdV-4 entry into LMH cells depended on clathrin. By using the inhibitor dynasore, we showed that dynamin was required for FAdV-4 entry. In addition, we found that FAdV-4 entry was dependent on membrane cholesterol, while neither the knockdown of caveolin nor the inhibition of a tyrosine kinase-based signalling cascade affected FAdV-4 infection. These results suggested that FAdV-4 entry required cholesterol but not caveolae. We also found that macropinocytosis played a role, and phosphatidylinositol 3-kinase (PI3K) was required for FAdV-4 internalization. However, inhibitors of endosomal acidification did not prevent FAdV-4 entry. Taken together, our findings demonstrate that FAdV-4 enters LMH cells through dynamin- and cholesterol-dependent clathrin-mediated endocytosis, accompanied by the involvement of macropinocytosis requiring PI3K. Our work potentially provides insight into the entry mechanisms of other avian adenoviruses. |
| first_indexed | 2024-04-09T22:42:40Z |
| format | Article |
| id | doaj.art-71d23168825f4908a0111320edbd8bc7 |
| institution | Directory Open Access Journal |
| issn | 1297-9716 |
| language | English |
| last_indexed | 2024-04-09T22:42:40Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj.art-71d23168825f4908a0111320edbd8bc72023-03-22T12:04:09ZengBMCVeterinary Research1297-97162023-03-0154111410.1186/s13567-023-01155-zFowl adenovirus serotype 4 enters leghorn male hepatocellular cells via the clathrin-mediated endocytosis pathwayTing Wang0Lizhen Wang1Wei Li2Xiaolan Hou3Wenchi Chang4Bo Wen5Shuizhong Han6Yan Chen7Xuefeng Qi8Jingyu Wang9College of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityAbstract Hepatitis-hydropericardium syndrome (HHS) induced by fowl adenovirus serotype-4 (FAdV-4) has caused large economic losses to the world poultry industry in recent years. HHS is characterized by pericardial effusion and hepatitis, manifesting as a swollen liver with focal necroses and petechial haemorrhage. However, the process of FAdV-4 entry into hepatic cells remains largely unknown. In this paper, we present a comprehensive study on the entry mechanism of FAdV-4 into leghorn male hepatocellular (LMH) cells. We first observed that FAdV-4 internalization was inhibited by chlorpromazine and clathrin heavy chain (CHC) knockdown, suggesting that FAdV-4 entry into LMH cells depended on clathrin. By using the inhibitor dynasore, we showed that dynamin was required for FAdV-4 entry. In addition, we found that FAdV-4 entry was dependent on membrane cholesterol, while neither the knockdown of caveolin nor the inhibition of a tyrosine kinase-based signalling cascade affected FAdV-4 infection. These results suggested that FAdV-4 entry required cholesterol but not caveolae. We also found that macropinocytosis played a role, and phosphatidylinositol 3-kinase (PI3K) was required for FAdV-4 internalization. However, inhibitors of endosomal acidification did not prevent FAdV-4 entry. Taken together, our findings demonstrate that FAdV-4 enters LMH cells through dynamin- and cholesterol-dependent clathrin-mediated endocytosis, accompanied by the involvement of macropinocytosis requiring PI3K. Our work potentially provides insight into the entry mechanisms of other avian adenoviruses.https://doi.org/10.1186/s13567-023-01155-zFAdV-4entryLMH cellsclathrinendocytosis |
| spellingShingle | Ting Wang Lizhen Wang Wei Li Xiaolan Hou Wenchi Chang Bo Wen Shuizhong Han Yan Chen Xuefeng Qi Jingyu Wang Fowl adenovirus serotype 4 enters leghorn male hepatocellular cells via the clathrin-mediated endocytosis pathway Veterinary Research FAdV-4 entry LMH cells clathrin endocytosis |
| title | Fowl adenovirus serotype 4 enters leghorn male hepatocellular cells via the clathrin-mediated endocytosis pathway |
| title_full | Fowl adenovirus serotype 4 enters leghorn male hepatocellular cells via the clathrin-mediated endocytosis pathway |
| title_fullStr | Fowl adenovirus serotype 4 enters leghorn male hepatocellular cells via the clathrin-mediated endocytosis pathway |
| title_full_unstemmed | Fowl adenovirus serotype 4 enters leghorn male hepatocellular cells via the clathrin-mediated endocytosis pathway |
| title_short | Fowl adenovirus serotype 4 enters leghorn male hepatocellular cells via the clathrin-mediated endocytosis pathway |
| title_sort | fowl adenovirus serotype 4 enters leghorn male hepatocellular cells via the clathrin mediated endocytosis pathway |
| topic | FAdV-4 entry LMH cells clathrin endocytosis |
| url | https://doi.org/10.1186/s13567-023-01155-z |
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