FIG 8.

Proposed model of regulation of VP35 function by ubiquitination. Upon virus recognition of EBOV infection, pattern recognition receptor (PRR) signaling promotes the synthesis of unanchored K48-linked polyubiquitin chains by the E3-ubiquitin ligase TRIM6. These polyubiquitin chains interact with IKKε and induce its oligomerization and downstream signaling to produce IFN-β (44). VP35 inhibits IFN-β at the level of RIG-I and the kinases TBK1 and IKKε (20). Ubiquitination of VP35 by TRIM6 promotes VP35-mediated polymerase activity and enhances virus replication.