title: An Orthogonal Proteomic Screen of Zika virus Reveals Specific Targeting of Neuronal Differentiation Factors
creator: Scaturro, Pietro
creator: Stukalov, Alexey
creator: Haas, Darya A.
creator: Cortese, Mirko
creator: Draganova, Kalina
creator: Płaszczyca, Anna
creator: Bartenschlager, Ralf
creator: Götz, Magdalena
creator: Pichlmair, Andreas
subject: ddc-570
subject: 570 Life sciences
description: 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.
publisher: Nature Publishing Group
date: 2018-09-03
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/26375/3/Scaturro_et_al_revised_manuscript_full.pdf
identifier: DOI:10.11588/heidok.00026375
identifier: urn:nbn:de:bsz:16-heidok-263758
identifier:   Scaturro, Pietro ; Stukalov, Alexey ; Haas, Darya A. ; Cortese, Mirko ; Draganova, Kalina ; Płaszczyca, Anna ; Bartenschlager, Ralf ; Götz, Magdalena ; Pichlmair, Andreas  (2018) An Orthogonal Proteomic Screen of Zika virus Reveals Specific Targeting of Neuronal Differentiation Factors.  Nature, 561.  pp. 253-257.  ISSN 1476-4687     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/26375/
relation: info:eu-repo/grantAgreement/EC/FP7/642434
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng