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. 2017:2017:1734151.
doi: 10.1155/2017/1734151. Epub 2017 Dec 12.

New Targets for Zika Virus Determined by Human-Viral Interactomic: A Bioinformatics Approach

Eduardo Esteves  1 , Nuno Rosa  1 , Maria José Correia  1 , Joel P Arrais  2 , Marlene Barros  1
Affiliations

New Targets for Zika Virus Determined by Human-Viral Interactomic: A Bioinformatics Approach

Eduardo Esteves et al. Biomed Res Int. 2017.

Abstract

Identifying ZIKV factors interfering with human host pathways represents a major challenge in understanding ZIKV tropism and pathogenesis. The integration of proteomic, gene expression and Protein-Protein Interactions (PPIs) established between ZIKV and human host proteins predicted by the OralInt algorithm identified 1898 interactions with medium or high score (≥0.7). Targets implicated in vesicular traffic and docking were identified. New receptors involved in endocytosis pathways as ZIKV entry targets, using both clathrin-dependent (17 receptors) and independent (10 receptors) pathways, are described. New targets used by the ZIKV to undermine the host's antiviral immune response are proposed based on predicted interactions established between the virus and host cell receptors and/or proteins with an effector or signaling role in the immune response such as IFN receptors and TLR. Complement and cytokines are proposed as extracellular potential interacting partners of the secreted form of NS1 ZIKV protein. Altogether, in this article, 18 new human targets for structural and nonstructural ZIKV proteins are proposed. These results are of great relevance for the understanding of viral pathogenesis and consequently the development of preventive (vaccines) and therapeutic targets for ZIKV infection management.

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Figures

Figure 1
Figure 1
Network of OralInt predicted PPIs (score ≥ 0.9) established between ZIKV proteins (blue) and human proteins (orange). The size of the node denotes the degree (number of interactions established). Red denotes underexpressed and green overexpressed proteins. Expression data from Tang et al. 2016 [56]. Diagram generated with Cytoscape V3.5.0 [59].
Figure 2
Figure 2
Diagram representing membrane and cytosolic targets of ZIKV used for host cell entry and immune response modulation. Information was obtained from OralInt predicted PPIs and the literature [–64].
Figure 3
Figure 3
Summary diagram of the proposed ZIKV targets considering the intra- and extracellular localization of the viral proteins during the infection cycle. Scores of the OralInt predicted PPIs are presented next to each human protein target and refer to interaction with the specific ZIKV protein. The proposed membrane orientation of the ZIKV proteins was modified from Figure 25.4 in Shi and Gao (2017) [54].
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