Novel Function of Avian p53 in Binding to ALV-J LTR Contributes to Its Antiviral Roles
Yueyue Duan,
Liyan Cao,
Cong Yuan,
Xuepeng Suo,
Xiangyu Kong,
Yulong Gao,
Xiangtong Li,
Haixue Zheng,
Xiaomei Wang,
Qi Wang
Affiliations
Yueyue Duan
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China
Liyan Cao
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Cong Yuan
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Xuepeng Suo
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Xiangyu Kong
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Yulong Gao
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China
Xiangtong Li
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Haixue Zheng
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
Xiaomei Wang
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China
Qi Wang
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
ABSTRACT Accumulating evidence suggests that p53 is involved in viral infection. However, it remains elusive whether avian p53 orchestrates avian leukosis virus (ALV) replication. We showed that p53 recruits the histone deacetylase 1 and 2 (HDAC1/2) complex to the ALV promoter to shut off ALV's promoter activity and viral replication. HDAC1/2 binding to the ALV promoter was abolished in the absence of p53. Moreover, we collected samples in ALV-infected chickens and found that the acetylation status of ALV-bound H3 and H4 histones correlated with ALV viremia. HDAC inhibitors (HDACi) potently increase ALV replication, but HDACi-promoted viral replication is dramatically reduced in cells with p53 depletion. These data demonstrate that p53 is critical for inhibition ALV replication and suggest that future studies of ALV replication need to account for the potential effects of p53 activity. IMPORTANCE Rous sarcoma virus (RSV)/ALV was the first retrovirus to be discovered, which was really the first hint that cancer, or a tumor, could be transmitted by a virus. The specific mechanisms that regulate ALV replication during infection remain poorly understood. Here, we show that avian p53 and HDAC complex inhibit ALV promoter activity and replication, and p53 inhibits ALV replication through binding to the ALV promoter. We demonstrated that the acetylation status of ALV-bound H3 and H4 histones correlates with ALV viremia level using clinical samples collected from commercial poultry. These findings identify both p53-mediated inhibition on ALV replication and a potential role for virus-induced tumorigenesis.
