title: Phosphorylation of Ebola virus VP30 influences the composition of the viral nucleocapsid complex: impact on viral transcription and replication.
abstract: Ebola virus is a non-segmented negative-sense RNA virus causing severe hemorrhagic fever with high fatality rates in humans and nonhuman primates. For transcription of the viral genome four viral proteins are essential: the nucleoprotein NP, the polymerase L, the polymerase cofactor VP35, and VP30. VP30 represents an essential Ebola virus-specific transcription factor whose activity is regulated via its phosphorylation state. In contrast to viral transcription, VP30 is not required for viral replication. Using a minigenome assay, we show that phosphorylation of VP30 inhibits viral transcription while viral replication is increased. Concurrently, phosphorylation of VP30 reciprocally regulates a newly described interaction of VP30 with VP35, and strengthens the interaction with NP. Our results indicate a critical role of VP30 phosphorylation for viral transcription and replication, suggesting a mechanism by which VP30 phosphorylation modulates the composition of the viral polymerase complex presumably forming a transcriptase in the presence of non-phosphorylated VP30 or a replicase in the presence of phosphorylated VP30.
authors.affiliation: Institut für Virologie, Philipps-Universität Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Biedenkopf
authors.forename: Bettina
authors.initials: B
authors.lastname: Hartlieb
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoenen
authors.forename: Stephan
authors.initials: S
authors.lastname: Becker
mesh_terms: D029043:Ebolavirus / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D019251:Nucleocapsid / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D014157:Transcription Factors; C479897:VP30 protein, ebola virus; D014764:Viral Proteins