TY  - JOUR
JF  - Nature
TI  - An Orthogonal Proteomic Screen of Zika virus Reveals Specific Targeting of Neuronal Differentiation Factors
N1  - 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
A1  - Scaturro, Pietro
A1  - Stukalov, Alexey
A1  - Haas, Darya A.
A1  - Cortese, Mirko
A1  - Draganova, Kalina
A1  - P?aszczyca, Anna
A1  - Bartenschlager, Ralf
A1  - Götz, Magdalena
A1  - Pichlmair, Andreas
EP  - 257
CY  - London
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/26375/
SN  - 1476-4687
PB  - Nature Publishing Group
AV  - public
VL  - 561
N2  - 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.
SP  - 253
KW  - embrionic stem-cells
KW  -  Zika virus
KW  -  Dengue virus
KW  -  phosphoproteomics
KW  -  differentiation
KW  -  enrichment
KW  -  infection
KW  -  platform
KW  -  genome
Y1  - 2018/09/03/
ID  - heidok26375
ER  -