Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses

Abstract The intracellular actions of interferon (IFN)-regulated proteins, including IFN-induced proteins with tetratricopeptide repeats (IFITs), attribute a major component of the protective antiviral host defense. Here we applied genomics approaches to annotate the chicken IFIT locus and currently...

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Autores principales:	Diwakar Santhakumar, Mohammed Abdel Mohsen Shahaat Rohaim, Hussein A. Hussein, Pippa Hawes, Helena Lage Ferreira, Shahriar Behboudi, Munir Iqbal, Venugopal Nair, Clarice W. Arns, Muhammad Munir
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e6e787f4a73461aa400c17e1ecfab18
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spelling	oai:doaj.org-article:8e6e787f4a73461aa400c17e1ecfab182021-12-02T15:08:55ZChicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses10.1038/s41598-018-24905-y2045-2322https://doaj.org/article/8e6e787f4a73461aa400c17e1ecfab182018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24905-yhttps://doaj.org/toc/2045-2322Abstract The intracellular actions of interferon (IFN)-regulated proteins, including IFN-induced proteins with tetratricopeptide repeats (IFITs), attribute a major component of the protective antiviral host defense. Here we applied genomics approaches to annotate the chicken IFIT locus and currently identified a single IFIT (chIFIT5) gene. The profound transcriptional level of this effector of innate immunity was mapped within its unique cis-acting elements. This highly virus- and IFN-responsive chIFIT5 protein interacted with negative sense viral RNA structures that carried a triphosphate group on its 5′ terminus (ppp-RNA). This interaction reduced the replication of RNA viruses in lentivirus-mediated IFIT5-stable chicken fibroblasts whereas CRISPR/Cas9-edited chIFIT5 gene knockout fibroblasts supported the replication of RNA viruses. Finally, we generated mosaic transgenic chicken embryos stably expressing chIFIT5 protein or knocked-down for endogenous chIFIT5 gene. Replication kinetics of RNA viruses in these transgenic chicken embryos demonstrated the antiviral potential of chIFIT5 in ovo. Taken together, these findings propose that IFIT5 specifically antagonize RNA viruses by sequestering viral nucleic acids in chickens, which are unique in innate immune sensing and responses to viruses of both poultry and human health significance.Diwakar SanthakumarMohammed Abdel Mohsen Shahaat RohaimHussein A. HusseinPippa HawesHelena Lage FerreiraShahriar BehboudiMunir IqbalVenugopal NairClarice W. ArnsMuhammad MunirNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-20 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Diwakar Santhakumar Mohammed Abdel Mohsen Shahaat Rohaim Hussein A. Hussein Pippa Hawes Helena Lage Ferreira Shahriar Behboudi Munir Iqbal Venugopal Nair Clarice W. Arns Muhammad Munir Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses
description	Abstract The intracellular actions of interferon (IFN)-regulated proteins, including IFN-induced proteins with tetratricopeptide repeats (IFITs), attribute a major component of the protective antiviral host defense. Here we applied genomics approaches to annotate the chicken IFIT locus and currently identified a single IFIT (chIFIT5) gene. The profound transcriptional level of this effector of innate immunity was mapped within its unique cis-acting elements. This highly virus- and IFN-responsive chIFIT5 protein interacted with negative sense viral RNA structures that carried a triphosphate group on its 5′ terminus (ppp-RNA). This interaction reduced the replication of RNA viruses in lentivirus-mediated IFIT5-stable chicken fibroblasts whereas CRISPR/Cas9-edited chIFIT5 gene knockout fibroblasts supported the replication of RNA viruses. Finally, we generated mosaic transgenic chicken embryos stably expressing chIFIT5 protein or knocked-down for endogenous chIFIT5 gene. Replication kinetics of RNA viruses in these transgenic chicken embryos demonstrated the antiviral potential of chIFIT5 in ovo. Taken together, these findings propose that IFIT5 specifically antagonize RNA viruses by sequestering viral nucleic acids in chickens, which are unique in innate immune sensing and responses to viruses of both poultry and human health significance.
format	article
author	Diwakar Santhakumar Mohammed Abdel Mohsen Shahaat Rohaim Hussein A. Hussein Pippa Hawes Helena Lage Ferreira Shahriar Behboudi Munir Iqbal Venugopal Nair Clarice W. Arns Muhammad Munir
author_facet	Diwakar Santhakumar Mohammed Abdel Mohsen Shahaat Rohaim Hussein A. Hussein Pippa Hawes Helena Lage Ferreira Shahriar Behboudi Munir Iqbal Venugopal Nair Clarice W. Arns Muhammad Munir
author_sort	Diwakar Santhakumar
title	Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses
title_short	Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses
title_full	Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses
title_fullStr	Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses
title_full_unstemmed	Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses
title_sort	chicken interferon-induced protein with tetratricopeptide repeats 5 antagonizes replication of rna viruses
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8e6e787f4a73461aa400c17e1ecfab18
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Chicken Interferon-induced Protein with Tetratricopeptide Repeats 5 Antagonizes Replication of RNA Viruses

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