title: Modulation of p53 cellular function and cell death by African swine fever virus.
abstract: Modulation of the activity of tumor suppressor p53 is a key event in the replication of many viruses. We have studied the function of p53 in African swine fever virus (ASFV) infection by determining the expression and activity of this transcription factor in infected cells. p53 levels are increased at early times of infection and are maintained throughout the infectious cycle. The protein is transcriptionally active, stabilized by phosphorylation, and localized in the nucleus. p53 induces the expression of p21 and Mdm2. Strikingly, these two proteins are located at the cytoplasmic virus factories. The retention of Mdm2 at the factory may represent a viral mechanism to prevent p53 inactivation by the protein. The expression of apoptotic proteins, such as Bax or active caspase-3, is also increased following ASFV infection, although the increase in caspase-3 does not appear to be, at least exclusively, p53 dependent. Bax probably plays a role in the induction of apoptosis in the infected cells, as suggested by the release of cytochrome c from the mitochondria. The significance of p21 induction and localization is discussed in relation to the shutoff of cellular DNA synthesis that is observed in ASFV-infected cells.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Universidad Autonoma, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Aitor G
authors.initials: AG
authors.lastname: Granja
authors.forename: María L
authors.initials: ML
authors.lastname: Nogal
authors.forename: Carolina
authors.initials: C
authors.lastname: Hurtado
authors.forename: José
authors.initials: J
authors.lastname: Salas
authors.forename: María L
authors.initials: ML
authors.lastname: Salas
authors.forename: Angel L
authors.initials: AL
authors.lastname: Carrascosa
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Revilla
mesh_terms: D000358:African Swine Fever Virus / Q000472:pathogenicity*; D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D005786:Gene Expression Regulation; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014709:Vero Cells / Q000821:virology
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2