Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 3 September 2019 / Approved: 7 September 2019 / Online: 7 September 2019 (00:18:39 CEST)

A peer-reviewed article of this Preprint also exists.

Golubeva, V.A.; Nepomuceno, T.C.; 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. Network of Interactions between ZIKA Virus Non-Structural Proteins and Human Host Proteins. Cells 2020, 9, 153. Golubeva, V.A.; Nepomuceno, T.C.; 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. Network of Interactions between ZIKA Virus Non-Structural Proteins and Human Host Proteins. Cells 2020, 9, 153.

Abstract

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. 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, this data can be used as a resource for future characterization of ZIKV infection biology and help create a basis for the discovery of drugs which may disrupt the interaction and reduce the health damage to the fetus.

Keywords

ZIKV; protein-protein interaction; non-structural viral proteins; network

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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