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Predicted protein interactions of IFITMs may shed light on mechanisms of Zika virus-induced microcephaly and host invasion

Ganapathiraju, Madhavi K and Karunakaran, Kalyani B and Correa-Menéndez, Josefina (2017) Predicted protein interactions of IFITMs may shed light on mechanisms of Zika virus-induced microcephaly and host invasion. In: F1000Research, 5 . ISSN 2046-1402

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Official URL: https://doi.org/10.12688/f1000research.9364.2


After the first reported case of Zika virus (ZIKV) 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 ZIKV. 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 the 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 (toll-like receptor 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 (neural tube closure, embryonic skeletal system development) that are associated with these interactors. Our novel PPIs associate cilia dysfunction in ependymal cells to microcephaly, and may also shed light on potential targets of ZIKV for host invasion by immunosuppression and cytoskeletal rearrangements. These results could help direct future research in elucidating the mechanisms underlying host defense to ZIKV and other flaviviruses.

Item Type: Journal Article
Publication: F1000Research
Publisher: Faculty of 1000 Ltd
Additional Information: The Copyright of this article belongs to the Authors.
Keywords: Interferon-inducible transmembrane proteins; Protein interaction; Virus infection; Zika; CD28 antigen; IFITM1 protein; IFITM3 protein; membrane protein; toll like receptor; unclassified drug; actin filament; Article; controlled study; dendritic cell; embryo development; ependyma cell; helper cell; host pathogen interaction; host resistance; intracellular signaling; microcephaly; molecular interaction; natural killer cell; nonhuman; prediction; protein database; protein determination; protein function; protein protein interaction; Zika virus
Department/Centre: Division of Interdisciplinary Sciences > Supercomputer Education & Research Centre
Date Deposited: 17 Jun 2022 07:37
Last Modified: 17 Jun 2022 07:37
URI: https://eprints.iisc.ac.in/id/eprint/73518

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