Abstract
After the first reported case of Zika virus in Brazil, in 2015, a significant increase in the reported cases of microcephaly was observed. Microcephaly is a neurological condition in which the infant's head is significantly smaller with complications in brain development. Recently, two small membrane-associated interferon-inducible transmembrane proteins (IFITM1 and IFITM3) have been shown to repress members of the flaviviridae family which includes the Zika virus. However, the exact mechanisms leading to the inhibition of the virus are yet unknown. Here, we assembled an interactome of IFITM1 and IFITM3 with known protein-protein interactions (PPIs) collected from publicly available databases and novel PPIs predicted using High-confidence Protein-Protein Interaction Prediction (HiPPIP) model. We analyzed the functional and pathway associations of the interacting proteins, and found that there are several immunity pathways (interferon signaling, cd28 signaling in T-helper cells crosstalk between dendritic cells and natural killer cells), neuronal pathways (axonal guidance signaling, neural tube closure and actin cytoskeleton signaling) and developmental pathways that are associated with these interactors. These results could help direct future research in elucidating the mechanisms underlying the viral immunity to Zika virus and other flaviviruses.
Highlights
The Zika virus (ZIKV) is a flavivirus that was initially isolated from rhesus monkeys in 1947 and was first reported in humans in 19521
This study demonstrated that ZIKV infects human embryonic cortical neural progenitor cells, leading to attenuated population growth mediated by virally induced caspase-3-mediated apoptosis and cell-cycle dysregulation[14]
We assembled the protein-protein interactions (PPIs) of IFITM1 and IFITM3 (Figure 1) by computing novel PPIs using High-confidence Protein-Protein Interaction Prediction (HiPPIP) model and collecting known PPIs from publicly available databases, Human Protein Reference Database (HPRD) and Biological General Repository for Interaction Dataset (BioGRID)[23,24]
Summary
The Zika virus (ZIKV) is a flavivirus that was initially isolated from rhesus monkeys in 1947 and was first reported in humans in 19521. The virus has rapidly spread across the Americas and has been declared a ‘global emergency’ by the World Health Organization[4] It is mostly transmitted by mosquitoes and clinical manifestations include rash, mild fever, arthralgia, conjunctivitis, myalgia, and headaches. In a study with human induced pluripotency stem cells, the mechanism of ZIKV related cell death has been elucidated. This study demonstrated that ZIKV infects human embryonic cortical neural progenitor cells (hNPCs), leading to attenuated population growth mediated by virally induced caspase-3-mediated apoptosis and cell-cycle dysregulation[14]. We applied HiPPIP model to discover novel PPIs of IFITM1 and IFITM3, to potentially accelerate the discovery of the mechanism by which they inhibit ZIKV and other viral infections
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
