title: An RS motif within the Epstein-Barr virus BLRF2 tegument protein is phosphorylated by SRPK2 and is important for viral replication.
abstract: Epstein-Barr virus (EBV) is a gammaherpesvirus that causes infectious mononucleosis, B cell lymphomas, and nasopharyngeal carcinoma. Many of the genes required for EBV virion morphogenesis are found in all herpesviruses, but some are specific to gammaherpesviruses. One of these gamma-specific genes, BLRF2, encodes a tegument protein that has been shown to be essential for replication in other gammaherpesviruses. In this study, we identify BLRF2 interacting proteins using binary and co-complex protein assays. Serine/Arginine-rich Protein Kinase 2 (SRPK2) was identified by both assays and was further shown to phosphorylate an RS motif in the BLRF2 C-terminus. Mutation of this RS motif (S148A+S150A) abrogated the ability of BLRF2 to support replication of a murine gammaherpesvirus 68 genome lacking the BLRF2 homolog (ORF52). We conclude that the BLRF2 RS motif is phosphorylated by SRPK2 and is important for viral replication.
authors: The Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Melissa
authors: M
authors: Duarte
authors: Lili
authors: L
authors: Wang
authors: Michael A
authors: MA
authors: Calderwood
authors: Guillaume
authors: G
authors: Adelmant
authors: Makoto
authors: M
authors: Ohashi
authors: Jennifer
authors: J
authors: Roecklein-Canfield
authors: Jarrod A
authors: JA
authors: Marto
authors: David E
authors: DE
authors: Hill
authors: Hongyu
authors: H
authors: Deng
authors: Eric
authors: E
authors: Johannsen
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005816:Genetic Complementation Test; D004854:Herpesvirus 4, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D012326:RNA Splicing; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D050505:Mutant Proteins; D014764:Viral Proteins; D017346:Protein Serine-Threonine Kinases; C110522:SRPK2 protein, human