title: The ORF4 protein of porcine circovirus type 2 antagonizes apoptosis by stabilizing the concentration of ferritin heavy chain through physical interaction.
abstract: Porcine circovirus type 2 (PCV2) is the primary aetiological agent of porcine circovirus-associated disease in swine. The mechanism of PCV2 pathogenesis remains largely unknown. A newly identified viral protein of PCV2, ORF4, has been suggested to be involved in virus-induced apoptosis. However, there is still no information regarding the molecular mechanism by which ORF4 regulates apoptosis. In this study, we reveal that a physical interaction between the PCV2 ORF4 protein and ferritin heavy chain (FHC) in the cytoplasm of host cells reduced the cellular concentration of FHC. The ORF4-mediated reduction of FHC inhibited reactive oxygen species accumulation in PCV2-infected cells. Consequently, the ORF4 protein inhibited apoptosis in host cells. This may be the first report to describe the mechanism of ORF4 cytoprotection against apoptosis during the early stages of PCV2 infection.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, PR China.
authors.forename: Qizhuang
authors.initials: Q
authors.lastname: Lv
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, PR China.
authors.forename: Kangkang
authors.initials: K
authors.lastname: Guo
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, PR China.
authors.forename: Guangfang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, PR China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D018173:Circoviridae Infections / Q000821:virology; D017925:Circovirus / Q000145:classification / Q000235:genetics*; D019610:Cytoprotection / Q000235:genetics*; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D034421:Sus scrofa / Q000821:virology*; D013552:Swine; D013553:Swine Diseases / Q000821:virology
chemical_list: D017874:Immediate-Early Proteins; C000618995:ORF4 protein, porcine circovirus type 2; D017382:Reactive Oxygen Species; D001052:Apoferritins