eprintid: 26375
rev_number: 45
eprint_status: archive
userid: 4398
dir: disk0/00/02/63/75
datestamp: 2019-05-10 14:52:31
lastmod: 2024-07-27 08:59:51
status_changed: 2019-05-10 14:52:31
type: article
metadata_visibility: show
creators_name: Scaturro, Pietro
creators_name: Stukalov, Alexey
creators_name: Haas, Darya A.
creators_name: Cortese, Mirko
creators_name: Draganova, Kalina
creators_name: Płaszczyca, Anna
creators_name: Bartenschlager, Ralf
creators_name: Götz, Magdalena
creators_name: Pichlmair, Andreas
title: An Orthogonal Proteomic Screen of Zika virus Reveals Specific Targeting of Neuronal Differentiation Factors
subjects: ddc-570
divisions: i-911700
keywords: embrionic stem-cells, Zika virus, Dengue virus, phosphoproteomics, differentiation, enrichment, infection, platform, genome
cterms_swd: Zika-Virus
cterms_swd: Denguevirus
cterms_swd: Protein
cterms_swd: Genom
note: 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
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.
date: 2018-09-03
publisher: Nature Publishing Group
id_scheme: DOI
id_number: 10.11588/heidok.00026375
fp7_project_id: 642434
ppn_swb: 1666405469
own_urn: urn:nbn:de:bsz:16-heidok-263758
language: eng
bibsort: SCATURROPIANORTHOGON20180903
full_text_status: public
publication: Nature
volume: 561
place_of_pub: London
pagerange: 253-257
issn: 1476-4687
citation:   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     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/26375/3/Scaturro_et_al_revised_manuscript_full.pdf