Phosphorylation of Ebola virus VP30 influences the composition of the viral nucleocapsid complex: impact on viral transcription and replication.

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.