Zika virus capsid protein C (ZIKV-C) interactors network mapped by proteomic analysis of human neural stem cells expressing FLAG-tagged C protein

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Abstract Zika virus is a teratogenic pathogen belonging to the Flaviviridae family. It possesses the ability to penetrate the placenta and affect the brain development of a fetus, resulting in microcephaly and functional impairments. Mechanisms of this neurotoxicity are still unclear, but capsid proteins of Zika and related viruses are known to exert apoptotic effect in different types of cells, including neurons. To explore the pathways affected by the presence of ZIKV-C, we have performed MS-based interactomic experiment in human neural stem cells and managed to identify 149 putative interactors. Our results indicate that the nucleus (especially the nucleolus) and the mitochondria are the main sites of interaction of protein C with host proteins. A number of the proteins we identified have significant links to diseases of the nervous system, including neurodevelopmental diseases. Furthermore, for the first time, we have identified MAM-domain containing glycosylphosphatidylinositol anchor protein 1, T-complex protein 1 subunit beta, lysine-tRNA ligase, calumenin as particularly abundant ZIKV protein C interactors. Data are available via ProteomeXchange with identifier PXD064412.

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