An orthogonal proteomic survey uncovers novel Zika virus host factors

Pietro Scaturro (), Alexey Stukalov, Darya A. Haas, Mirko Cortese, Kalina Draganova, Anna Płaszczyca, Ralf Bartenschlager, Magdalena Götz and Andreas Pichlmair ()
Additional contact information
Pietro Scaturro: Max-Planck Institute of Biochemistry, Innate Immunity Laboratory
Alexey Stukalov: Max-Planck Institute of Biochemistry, Innate Immunity Laboratory
Darya A. Haas: Max-Planck Institute of Biochemistry, Innate Immunity Laboratory
Mirko Cortese: University of Heidelberg
Kalina Draganova: Helmholtz Center Munich
Anna Płaszczyca: University of Heidelberg
Ralf Bartenschlager: University of Heidelberg
Magdalena Götz: Helmholtz Center Munich
Andreas Pichlmair: Max-Planck Institute of Biochemistry, Innate Immunity Laboratory

Nature, 2018, vol. 561, issue 7722, 253-257

Abstract: 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.

Keywords: Zika Virus (ZIKV); ZIKV Infection; Neuronal Ceroid Lipofuscinoses Proteins (CLN6); DNA Was Stained With 4′; 6-diamidino-2-phenylindole (DAPI); ZIKV Replication (search for similar items in EconPapers)
Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0484-5 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:561:y:2018:i:7722:d:10.1038_s41586-018-0484-5

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-018-0484-5

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().