In Silico Analysis of Possible Interaction between Host Genomic Transcription Factors (TFs) and Zika Virus (ZikaSPH2015) Strain with Combinatorial Gene Regulation; Virus Versus Host-The Game Reloaded.

Massimiliano Chetta,Nenad Bukvic,Laura Vicari,Marina Tarsitano,Annalisa Saracino

doi:10.3390/pathogens10010069

Abstract

In silico analysis is a promising approach for understanding biological events in complex diseases. Herein we report on the innovative computational workflow allowed to highlight new direct interactions between human transcription factors (TFs) and an entire genome of virus ZikaSPH2015 strain in order to identify the occurrence of specific motifs on a genomic Zika Virus sequence that is able to bind and, therefore, sequester host’s TFs. The analysis pipeline was performed using different bioinformatics tools available online (free of charge). According to obtained results of this in silico analysis, it is possible to hypothesize that these TFs binding motifs might be able to explain the complex and heterogeneous phenotype presentation in Zika-virus-affected fetuses/newborns, as well as the less severe condition in adults. Moreover, the proposed in silico protocol identified thirty-three different TFs identical to the distribution of TFBSs (Transcription Factor Binding Sites) on ZikaSPH2015 strain, potentially able to influence genes and pathways with biological functions confirming that this approach could find potential answers on disease pathogenesis.

Highlights

The Zika virus (ZIKV) is a positive-sense, single-strand RNA arbovirus belonging to the Flaviviridae family, genus Flavivirus, which includes other well known viruses, such as yellow fever, the dengue virus and the West Nile virus [1]
Based on the performed in silico analysis, it was possible to identify the occurrence of specific motifs in the ZikaSPH2015 strain
Even though many studies are concentrated on the molecular mechanism of ZIKV infection, the exact mechanisms that induce the complex symptomatology, including microcephaly and brain anomalies in fetuses, remain unclear

Summary

Introduction

The Zika virus (ZIKV) is a positive-sense, single-strand RNA arbovirus belonging to the Flaviviridae family, genus Flavivirus, which includes other well known viruses, such as yellow fever, the dengue virus and the West Nile virus [1]. Because fetal complications resulting from ZIKV infection contracted in pregnancy (first trimester) have been demonstrated [3,4], scientific interest has been increasing. Brazil was the first country where important fetal development issues were described, including microcephaly babies, with a high number of case notifications (2010: n = 153, 2011: n = 139, 2012: n = 175, 2013: n = 167 and 2014: n = 147), high variability amongst different regions has been recorded [5]

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Results

Conclusion