title: Phosphorylation of human polyomavirus BK agnoprotein at Ser-11 is mediated by PKC and has an important regulative function.
abstract: The human polyomavirus BK (BKV) genome encodes the capsid proteins VP1 to VP3 and the three regulatory proteins, large and small tumor-antigen and the agnoprotein. Agnoprotein is a phospho-protein, but phosphorylation sites, protein kinases that mediate phosphorylation, and the biological importance of phosphorylation for the life-cycle of BK virus remain unknown. Here, we show that protein kinase C phosphorylates BKV agnoprotein at serine-11. Replacing serine-11 by either non-phosphorylable alanine or phospho-mimicking aspartic acid reduced the ability of these mutants to propagate compared to wildtype virus. Moreover, both these mutants displayed altered expression of viral proteins, which resulted from changed transrepressive property and stability of the mutated agnoprotein. Our results indicate that BKV propagation is controlled by phosphorylation of the agnoprotein and may suggest that specific inhibition of protein kinases may be used as a therapeutic strategy to hamper BK virus infection.
authors.affiliation: University of Tromsø, Faculty of Medicine, Department of Microbiology and Virology, 9037 Tromsø, Norway. monaj@fagmed.uit.no
authors.forename: Mona
authors.initials: M
authors.lastname: Johannessen
authors.forename: Marit Renée
authors.initials: MR
authors.lastname: Myhre
authors.forename: Marte
authors.initials: M
authors.lastname: Dragset
authors.forename: Conny
authors.initials: C
authors.lastname: Tümmler
authors.forename: Ugo
authors.initials: U
authors.lastname: Moens
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001739:BK Virus / Q000502:physiology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000096:biosynthesis; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D014779:Virus Replication; D000086082:Viroporin Proteins
chemical_list: D011493:Protein Kinase C; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins