Unraveling viral protein-host membrane interaction for dengue and Zika

Abstract

Mosquito-borne flaviviruses, including dengue virus (DENV) and Zika virus (ZIKV), constitute a significant and escalating public health threat. Elucidating the mechanisms by which these flaviviruses subvert cellular processes through viral protein-host cell interactions provides critical insights into their replication and pathogenicity. Here, we present an analysis basedon anisotropy calculation across pixels in raster images to investigate differential protein interactions during nucleocytoplasmic shuttling. This methodology highlights regions of high and low anisotropy, suggesting differential protein-membrane interactions.Employing numerical simulations and confocal raster images, we use this method to investigate capsid (C) protein-host cell membrane interactions for DENV serotype 2 (DENV2) and ZIKV-transfected cells during C-protein nucleocytoplasmic shuttling.By 2D pair correlation analysis on infected cells, we demonstrated that the DENV2 C-protein exhibits a pronounced interaction with the host cell’s nuclear membrane. Furthermore, we identified a differential localization of C-protein for these viruses in the host cell. These findings highlight the significance of comparative viral protein-host interaction mapping in deciphering pathogenicmechanisms, particularly when combined with in vivo models. Given that dengue and Zika are two of the most significant human viral infections transmitted by arthropods, a thorough understanding of viral protein dynamics is imperative for developing novel antiviral strategies.