Network of Interactions between ZIKA Virus Non-Structural Proteins and Human Host Proteins.
ZIKV
network
non-structural viral proteins
protein–protein interaction
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
08 01 2020
08 01 2020
Historique:
received:
03
09
2019
revised:
20
12
2019
accepted:
01
01
2020
entrez:
16
1
2020
pubmed:
16
1
2020
medline:
5
2
2021
Statut:
epublish
Résumé
The Zika virus (ZIKV) is a mosquito-borne Flavivirus and can be transmitted through an infected mosquito bite or through human-to-human interaction by sexual activity, blood transfusion, breastfeeding, or perinatal exposure. After the 2015-2016 outbreak in Brazil, a strong link between ZIKV infection and microcephaly emerged. ZIKV specifically targets human neural progenitor cells, suggesting that proteins encoded by ZIKV bind and inactivate host cell proteins, leading to microcephaly. Here, we present a systematic annotation of interactions between human proteins and the seven non-structural ZIKV proteins corresponding to a Brazilian isolate. The interaction network was generated by combining tandem-affinity purification followed by mass spectrometry with yeast two-hybrid screens. We identified 150 human proteins, involved in distinct biological processes, as interactors to ZIKV non-structural proteins. Our interacting network is composed of proteins that have been previously associated with microcephaly in human genetic disorders and/or animal models. Further, we show that the protein inhibitor of activated STAT1 (PIAS1) interacts with NS5 and modulates its stability. This study builds on previously published interacting networks of ZIKV and genes related to autosomal recessive primary microcephaly to generate a catalog of human cellular targets of ZIKV proteins implicated in processes related to microcephaly in humans. Collectively, these data can be used as a resource for future characterization of ZIKV infection biology and help create a basis for the discovery of drugs that may disrupt the interaction and reduce the health damage to the fetus.
Identifiants
pubmed: 31936331
pii: cells9010153
doi: 10.3390/cells9010153
pmc: PMC7016862
pii:
doi:
Substances chimiques
NS5 protein, flavivirus
0
STAT1 Transcription Factor
0
STAT1 protein, human
0
Viral Nonstructural Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : P30 CA076292
Pays : United States
Déclaration de conflit d'intérêts
The authors declare that they have no conflicts of interest related to the contents of this article.
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