title: Sumoylation of the P protein at K254 plays an important role in growth of parainfluenza virus 5.
abstract: The P protein of parainfluenza virus 5 (PIV5) is an essential cofactor of the viral RNA-dependent RNA polymerase. Phosphorylation of the P protein can positively or negatively regulate viral gene expression, depending on the precise phosphorylation sites. Sumoylation, a process of adding small ubiquitin-like modifier (SUMO) to proteins posttranslationally, plays an important role in regulating protein function. In this study, we have found that the P protein of PIV5 was sumoylated with SUMO1 in both transfected and infected cells. The K254 residue of the P protein is within a consensus sumoylation motif. Mutation of the P protein at K254 to arginine (P-K254R) reduced PIV5 minigenome activity, as well as the sumoylation level of the P protein. Incorporation of K254R into a recombinant PIV5 (rPIV5-P-K254R) resulted in a virus that grew to a lower titer and had lower levels of viral RNA synthesis and protein expression than wild-type PIV5, suggesting that sumoylation of the P protein at K254 is important for PIV5 growth. Biochemical studies did not reveal any defect of P-K254R in its interactions with viral proteins NP and L or formation of homotetramers. We propose that sumoylation of the P protein at K254 regulates PIV5 gene expression through a host protein.
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, GA, USA.
authors.forename: Dengyun
authors.initials: D
authors.lastname: Sun
authors.forename: Pei
authors.initials: P
authors.lastname: Xu
authors.forename: Biao
authors.initials: B
authors.lastname: He
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000378:metabolism*; D016601:RNA-Binding Proteins; D019213:Rubulavirus / Q000254:growth & development / Q000502:physiology*; D025842:SUMO-1 Protein / Q000378:metabolism; D058207:Sumoylation; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C097018:P protein, Simian parainfluenza virus 5; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D014764:Viral Proteins; D008239:Lysine