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

Author(s)

Santhakumar, Diwakar ^{[1, 2]} ; Rohaim, Mohammed Abdel Mohsen Shahaat ^{[1, 2, 3]} ; Hussein, Hussein A. ^[3] ; Hawes, Pippa ^[1] ; Ferreira, Helena Lage ^[4] ; Behboudi, Shahriar ^{[1, 5]} ; Iqbal, Munir ^[1] ; Nair, Venugopal ^[1] ; Arns, Clarice W. ^[6] ; Munir, Muhammad ^{[1, 2]}

Affiliation

^[1] Pirbright Inst, Woking GU24 0NF, Surrey - England

^[2] Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster LA1 4YG - England

^[3] Cairo Univ, Fac Vet Med, Dept Virol, Giza 12211 - Egypt

^[4] Univ Sao Paulo, Campus Pirassununga, Sao Paulo - Brazil

^[5] Univ Surrey, Sch Vet Med, Dept Pathol & Infect Dis, Surrey - England

^[6] Univ Estadual Campinas, Inst Biol, Sao Paulo - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, MAY 1 2018.
• Web of Science Citations: 9

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. (AU)

• FAPESP's process: 14/50696-4 - Dissecting essential roles of chicken interferon stimulated genes in the pathobiology of poultry viruses
• Grantee: Clarice Weis Arns
• Support Opportunities: Regular Research Grants