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Participation of Extracellular Vesicles from Zika-Virus-Infected Mosquito Cells in the Modification of Naïve Cells’ Behavior by Mediating Cell-to-Cell Transmission of Viral Elements
Open AccessArticle

Network of Interactions between ZIKA Virus Non-Structural Proteins and Human Host Proteins

1
Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
2
Divisão de Pesquisa Clínica, Instituto Nacional de Câncer, Rio de Janeiro 20230-130, Brazil
3
Departamento de Bioquímica, Instituto de Química, Federal University of Rio de Janeiro, Rio de Janeiro 21941-909, Brazil
4
Cancer Biology PhD Program, University of South Florida, Tampa, FL 33612, USA
5
Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro 20230-130, Brazil
6
Proteomics and Metabolomics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
7
Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA
8
Instituto Federal do Rio de Janeiro-IFRJ, Rio de Janeiro 20270-021, Brazil
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(1), 153; https://doi.org/10.3390/cells9010153
Received: 3 September 2019 / Revised: 20 December 2019 / Accepted: 1 January 2020 / Published: 8 January 2020
(This article belongs to the Special Issue Zika Virus and Host Interactions)
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. View Full-Text
Keywords: ZIKV; protein–protein interaction; non-structural viral proteins; network ZIKV; protein–protein interaction; non-structural viral proteins; network
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Golubeva, V.A.; Nepomuceno, T.C.; de Gregoriis, G.; Mesquita, R.D.; Li, X.; Dash, S.; Garcez, P.P.; Suarez-Kurtz, G.; Izumi, V.; Koomen, J.; Carvalho, M.A.; Monteiro, A.N.A. Network of Interactions between ZIKA Virus Non-Structural Proteins and Human Host Proteins. Cells 2020, 9, 153.

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