Role of p53 in pseudorabies virus replication, pathogenicity, and host immune responses
Abstract As a key cellular transcription factor that plays a central role in cellular responses to a broad range of stress factors, p53 has generally been considered as a host cell restriction factor for various viral infections. However, the defined roles of p53 in pseudorabies virus (PRV) replicat...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Veterinary Research |
| Online Access: | http://link.springer.com/article/10.1186/s13567-019-0627-1 |
| _version_ | 1818145993232744448 |
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| author | Xun Li Wei Zhang Yunjia Liu Jiaxun Xie Chuanhuo Hu Xiaoye Wang |
| author_facet | Xun Li Wei Zhang Yunjia Liu Jiaxun Xie Chuanhuo Hu Xiaoye Wang |
| author_sort | Xun Li |
| collection | DOAJ |
| description | Abstract As a key cellular transcription factor that plays a central role in cellular responses to a broad range of stress factors, p53 has generally been considered as a host cell restriction factor for various viral infections. However, the defined roles of p53 in pseudorabies virus (PRV) replication, pathogenesis, and host responses remain unclear. In the present study, we initially constructed a p53 overexpressing a porcine kidney epithelial cell line (PK-15) to detect the effect of p53 on PRV replication in vitro. The results show that viral glycoprotein B (gB) gene copies and the titers of virus were significantly higher in p53 overexpressing PK-15 cells than in PK-15 and p53 inhibitor treated p53 overexpressing PK-15 cells. A similar result was also found in the p53 inhibitor PFT-α-treated PK-15 cells. We then examined the effects of p53 on PRV infection in vivo by using p53-knockout (p53−/−) mice. The results show that p53 knockout not only led to significantly reduced rates of mortality but also to reduced viral replication and development of viral encephalitis in the brains of mice following intracranial inoculation. Furthermore, we examined the effect of p53 knockout on the expression of the reported host cell regulators of PRV replication in the brains of mice by using RNA sequencing. The results show that p53 knockout downregulated the interferon (IFN) regulator genes, chemokine genes, and antiviral genes after PRV infection. This finding suggests that p53 positively regulates viral replication and pathogenesis both in vitro and in vivo. These findings offer novel targets of intrinsic host cell immunity for PRV infection. |
| first_indexed | 2024-12-11T12:12:17Z |
| format | Article |
| id | doaj.art-dbac140c018b434cb08c42d412bc6efa |
| institution | Directory Open Access Journal |
| issn | 1297-9716 |
| language | English |
| last_indexed | 2024-12-11T12:12:17Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj.art-dbac140c018b434cb08c42d412bc6efa2022-12-22T01:07:46ZengBMCVeterinary Research1297-97162019-02-0150111210.1186/s13567-019-0627-1Role of p53 in pseudorabies virus replication, pathogenicity, and host immune responsesXun Li0Wei Zhang1Yunjia Liu2Jiaxun Xie3Chuanhuo Hu4Xiaoye Wang5College of Animal Science and Technology, Guangxi UniversityDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical UniversityCollege of Animal Science and Technology, Guangxi UniversityCollege of Animal Science and Technology, Guangxi UniversityCollege of Animal Science and Technology, Guangxi UniversityCollege of Animal Science and Technology, Guangxi UniversityAbstract As a key cellular transcription factor that plays a central role in cellular responses to a broad range of stress factors, p53 has generally been considered as a host cell restriction factor for various viral infections. However, the defined roles of p53 in pseudorabies virus (PRV) replication, pathogenesis, and host responses remain unclear. In the present study, we initially constructed a p53 overexpressing a porcine kidney epithelial cell line (PK-15) to detect the effect of p53 on PRV replication in vitro. The results show that viral glycoprotein B (gB) gene copies and the titers of virus were significantly higher in p53 overexpressing PK-15 cells than in PK-15 and p53 inhibitor treated p53 overexpressing PK-15 cells. A similar result was also found in the p53 inhibitor PFT-α-treated PK-15 cells. We then examined the effects of p53 on PRV infection in vivo by using p53-knockout (p53−/−) mice. The results show that p53 knockout not only led to significantly reduced rates of mortality but also to reduced viral replication and development of viral encephalitis in the brains of mice following intracranial inoculation. Furthermore, we examined the effect of p53 knockout on the expression of the reported host cell regulators of PRV replication in the brains of mice by using RNA sequencing. The results show that p53 knockout downregulated the interferon (IFN) regulator genes, chemokine genes, and antiviral genes after PRV infection. This finding suggests that p53 positively regulates viral replication and pathogenesis both in vitro and in vivo. These findings offer novel targets of intrinsic host cell immunity for PRV infection.http://link.springer.com/article/10.1186/s13567-019-0627-1 |
| spellingShingle | Xun Li Wei Zhang Yunjia Liu Jiaxun Xie Chuanhuo Hu Xiaoye Wang Role of p53 in pseudorabies virus replication, pathogenicity, and host immune responses Veterinary Research |
| title | Role of p53 in pseudorabies virus replication, pathogenicity, and host immune responses |
| title_full | Role of p53 in pseudorabies virus replication, pathogenicity, and host immune responses |
| title_fullStr | Role of p53 in pseudorabies virus replication, pathogenicity, and host immune responses |
| title_full_unstemmed | Role of p53 in pseudorabies virus replication, pathogenicity, and host immune responses |
| title_short | Role of p53 in pseudorabies virus replication, pathogenicity, and host immune responses |
| title_sort | role of p53 in pseudorabies virus replication pathogenicity and host immune responses |
| url | http://link.springer.com/article/10.1186/s13567-019-0627-1 |
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