Analysis of the Zika and Japanese encephalitis virus NS5 interactomes.

Mosquito-borne flaviviruses, including dengue virus (DENV), Japanese encephalitis virus (JEV) and Zika virus (ZIKV), are major human pathogens. Among the flaviviral proteins, the non-structural protein 5 (NS5) is the largest, most conserved and major enzymatic component of the viral replication complex. Disruption of the common key NS5-host protein-protein interactions critical for viral replication could aid in the development of broad-spectrum anti-flaviviral therapeutics. Hundreds of NS5 interactors have been identified, but these are mostly DENV-NS5 interactors. To this end, we sought to investigate the JEV- and ZIKV-NS5 interactomes using EGFP immunoprecipitation with label-free quantitative mass spectrometry analysis. We report here a total of 137 NS5 interactors with a significant enrichment of spliceosomal and spliceosomal-associated proteins. The transcription complex Paf1C and phosphatase 6 were identified as common NS5-associated complexes. PAF1 was shown to play opposite roles in JEV and ZIKV ...