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An Orthogonal Proteomic Screen of Zika virus Reveals Specific Targeting of Neuronal Differentiation Factors

Scaturro, Pietro ; Stukalov, Alexey ; Haas, Darya A. ; Cortese, Mirko ; Draganova, Kalina ; Płaszczyca, Anna ; Bartenschlager, Ralf ; Götz, Magdalena ; Pichlmair, Andreas

In: Nature, 561 (3 September 2018), pp. 253-257. ISSN 1476-4687

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Abstract

Zika virus (ZIKV) has recently emerged as a global health concern owing to its widespread diffusion and its association with severe neurological symptoms and microcephaly in newborns1. However, the molecular mechanisms that are responsible for the pathogenicity of ZIKV remain largely unknown. Here we use human neural progenitor cells and the neuronal cell line SK-N-BE2 in an integrated proteomics approach to characterize the cellular responses to viral infection at the proteome and phosphoproteome level, and use affinity proteomics to identify cellular targets of ZIKV proteins. Using this approach, we identify 386 ZIKV-interacting proteins, ZIKV-specific and pan-flaviviral activities as well as host factors with known functions in neuronal development, retinal defects and infertility. Moreover, our analysis identified 1,216 phosphorylation sites that are specifically up- or downregulated after ZIKV infection, indicating profound modulation of fundamental signalling pathways such as AKT, MAPK-ERK and ATM-ATR and thereby providing mechanistic insights into the proliferation arrest elicited by ZIKV infection. Functionally, our integrative study identifies ZIKV host-dependency factors and provides a comprehensive framework for a system-level understanding of ZIKV-induced perturbations at the levels of proteins and cellular pathways.

Item Type: Article
Journal or Publication Title: Nature
Volume: 561
Publisher: Nature Publishing Group
Place of Publication: London
Date Deposited: 10 May 2019 14:52
Date: 3 September 2018
ISSN: 1476-4687
Page Range: pp. 253-257
Faculties / Institutes: Medizinische Fakultät Heidelberg > Department for Infectiology
Subjects: 570 Life sciences
Controlled Keywords: Zika-Virus, Denguevirus, Protein, Genom
Uncontrolled Keywords: embrionic stem-cells, Zika virus, Dengue virus, phosphoproteomics, differentiation, enrichment, infection, platform, genome
Additional Information: Final version has been published with revised title: "An orthogonal proteomic survey uncovers novel Zika virus host factors". https://www.nature.com/articles/s41586-018-0484-5
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