1. Basal Level p53 Suppresses Antiviral Immunity Against Foot-And-Mouth Disease Virus
- Author
-
Zhang Jie, Tianliang Zhang, Yongguang Zhang, Kailing Wang, Haotai Chen, Xin Gao, Xinsheng Liu, Kaishen Yao, Run Wu, Sun Yuefeng, and Linlin Qi
- Subjects
0301 basic medicine ,p53 ,Swine ,animal diseases ,viruses ,lcsh:QR1-502 ,Virus Replication ,Virus ,lcsh:Microbiology ,Article ,Cell Line ,03 medical and health sciences ,Gene Knockout Techniques ,0302 clinical medicine ,MDM2 ,Interferon ,Virology ,Cricetinae ,medicine ,Animals ,Transcription factor ,innate immunity ,Disease Resistance ,Innate immune system ,biology ,foot-and-mouth disease virus ,interferon ,biology.organism_classification ,Immunity, Innate ,030104 developmental biology ,Infectious Diseases ,Viral replication ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Foot-and-Mouth Disease ,Knockout mouse ,Host-Pathogen Interactions ,Foot-and-mouth disease virus ,Tumor Suppressor Protein p53 ,Viral load ,medicine.drug - Abstract
Tumor suppressor protein p53 (p53) is a master transcription factor that plays key roles in cell cycle arrest, apoptosis, senescence, and metabolism, as well as regulation of innate immunity during virus infection. In order to facilitate their replication and spreading, viruses have evolved to manipulate p53 function through different strategies, with some requiring active p53 while others demand reduction/inhibition of p53 activity. However, there are no clear-cut reports about the roles of p53 during the infection of foot-and-mouth disease virus (FMDV), the causative agent of a highly contagious foot-and-mouth disease (FMD) of cloven-hoofed animals. Here we showed that p53 level was dynamically regulated during FMDV infection, being degraded at the early infection stage but recovered to the basal level at the late stage. Cells depleted of p53 showed inhibited FMDV replication and enhanced expression of the immune-related genes, whereas overexpression of p53 didn&rsquo, t affect the viral replication. Viral challenge assay with p53 knockout mice obtained similar results, with viral load decreased, histopathological changes alleviated, and lifespan extended in the p53 knockout mice. Together, these data demonstrate that basal level p53 is required for efficient FMDV replication by suppressing the innate immunity.
- Published
- 2019