Novel antagonistic mechanisms between human Sec3 exocyst and flavivirus capsid protein

Abstract

Flavivirus capsid (C) protein is a key structural component of virus particles. However, the role of C protein in the pathogenesis of flaviviruses is poorly understood. To examine whether flavivirus C protein associates with cellular proteins and contribute to viral pathogenesis, flavivirus C proteins were screened against a human cDNA yeast two-hybrid library. This study identified human Sec3 exocyst protein (hSec3p) as a novel interacting partner of flavivirus C protein. Mutagenesis studies showed that SH2 domain-binding motif of hSec3p binds to the first 15 amino acids of C protein. The hSec3p modulated virus production by affecting viral RNA transcription and translation through the sequestration of elongation factor 1 alpha (EF1alpha).¿This molecular discovery shed light on the protective role of hSec3p during flavivirus infection. This study also highlighted the antagonistic mechanism adopted by flavivirus C protein that can negatively regulate the formation of hSec3p-EF1alpha complex by degrading hSec3p via proteasome-mediated pathway.