Disease relevance of VP35

• This system was used to exchange the EBOV Zaire and EBOV Reston nucleocapsid (NC) proteins NP, VP35, VP30, and L, which catalyze replication and transcription [1].

High impact information on VP35

• Importantly, we show that the recombinant viruses were attenuated for growth in cell culture and that they activated IRF-3 and IRF-3-inducible gene expression at levels higher than that for Ebola virus containing wild-type VP35 [2].
• In the context of Ebola virus pathogenesis, VP35 may function to limit early IFN-beta production and other antiviral signals generated from cells at the primary site of infection, thereby slowing down the host's ability to curb virus replication and induce adaptive immunity [2].
• We now show that VP35 inhibits virus infection-induced transcriptional activation of IFN regulatory factor 3 (IRF-3)-responsive mammalian promoters and that VP35 does not block signaling from the IFN-alpha/beta receptor [3].
• Exchange of NP, VP35, and L between the two replication systems did not lead to detectable reporter gene expression [4].
• A 22-mer P-PMO designed to base pair with the translation start site region of EBOV VP35 positive-sense RNA generated sequence-specific and time- and dose-dependent inhibition of EBOV amplification in cell culture [5].

Biological context of VP35

• The ebolavirus VP35 protein antagonizes the cellular type I interferon response by blocking phosphorylation of IRF-3, a transcription factor that turns on the expression of a large number of antiviral genes [6].
• To identify the domain of VP35 responsible for interferon antagonism, we generated mutations within the VP35 gene and found that a C-terminal basic amino acid motif is required for inhibition of ISG56 reporter gene expression as well as IFN-beta production [6].

References