Mutation of Ebola virus VP35 Ser129 uncouples interferon antagonist and replication functions

MJ Morwitzer; A Corona; L Zinzula; E Fanunza; C Nigri; S Distinto; C Vornholt; V Kumar; E Tramontano; SP Reid

impaired ability to interact with the viral polymerase. . It has been shown that 523 VSV P protein must undergo phosphorylation-dependent homo-oligomerization to become 524 transcriptionally active (Gao and Lenard, 1995) . Consistent with these findings are the nanoDSF 525 results in this study which indicate that the VP35-S129A mutant possesses a higher degree of 526 flexibility at the level of the VP35 oligomerization domain, and severely decreases EBOV 527 minigenome activity. In addition, the oligomerization domain of MuV and hPIV3 P proteins has 528 been shown to have an enhancing effect on the P-L interaction, which further supports the 529 findings here (Choudhary et al., 2002 , Pickar et al., 2015 . 530 VP35 has been shown to be phosphorylated by IKKε and TBK-1 in vitro, which suggests the 531 possibility that its function may be modulated by these kinases (Prins et al., 2009) . In this case 532 VP35 exerts IFN-antagonist function by preventing TBK-1 and/or IKKε from activating 533 IRF3/IRF7. It has yet to be determined whether VP35 becomes phosphorylated in EBOV-534