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Article

Transgenic Chicks Expressing Interferon-Inducible Transmembrane Protein 1 (IFITM1) Restrict Highly Pathogenic H5N1 Influenza Viruses

1
Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YG, UK
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Department of Virology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt
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Department of Veterinary Pathology & Public Health, Faculty of Veterinary Medicine, Jordan University of Science and Technology (JUST), P.O. Box 3030, Irbid 22110, Jordan
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Department of Poultry Viral Vaccines, Veterinary Serum and Vaccine Research Institute (VSVRI), Agriculture Research Centre (ARC), Cairo 11435, Egypt
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Department of Virology, Faculty of Veterinary Medicine, University of Sadat City, Sadat 32897, Egypt
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Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt
*
Author to whom correspondence should be addressed.
Academic Editors: Maria Grazia Romanelli and Greta Forlani
Int. J. Mol. Sci. 2021, 22(16), 8456; https://doi.org/10.3390/ijms22168456
Received: 4 July 2021 / Revised: 2 August 2021 / Accepted: 3 August 2021 / Published: 6 August 2021
(This article belongs to the Special Issue Virus–Host Interaction and Cell Restriction Mechanisms)
Mammalian cells utilize a wide spectrum of pathways to antagonize the viral replication. These pathways are typically regulated by antiviral proteins and can be constitutively expressed but also exacerbated by interferon induction. A myriad of interferon-stimulated genes (ISGs) have been identified in mounting broad-spectrum antiviral responses. Members of the interferon-induced transmembrane (IFITM) family of proteins are unique among these ISGs due to their ability to prevent virus entry through the lipid bilayer into the cell. In the current study, we generated transgenic chickens that constitutively and stably expressed chicken IFITM1 (chIFITM1) using the avian sarcoma-leukosis virus (RCAS)-based gene transfer system. The challenged transgenic chicks with clinical dose 104 egg infective dose 50 (EID50) of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 (clade 2.2.1.2) showed 100% protection and significant infection tolerance. Although challenged transgenic chicks displayed 60% protection against challenge with the sub-lethal dose (EID50 105), the transgenic chicks showed delayed clinical symptoms, reduced virus shedding, and reduced histopathologic alterations compared to non-transgenic challenged control chickens. These finding indicate that the sterile defense against H5N1 HPAIV offered by the stable expression of chIFITM1 is inadequate; however, the clinical outcome can be substantially ameliorated. In conclusion, chIFITM proteins can inhibit influenza virus replication that can infect various host species and could be a crucial barrier against zoonotic infections. View Full-Text
Keywords: transgenic chickens; chIFITM1; HPAIV H5N1; zoonotic infections transgenic chickens; chIFITM1; HPAIV H5N1; zoonotic infections
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MDPI and ACS Style

Rohaim, M.A.; Al-Natour, M.Q.; Abdelsabour, M.A.; El Naggar, R.F.; Madbouly, Y.M.; Ahmed, K.A.; Munir, M. Transgenic Chicks Expressing Interferon-Inducible Transmembrane Protein 1 (IFITM1) Restrict Highly Pathogenic H5N1 Influenza Viruses. Int. J. Mol. Sci. 2021, 22, 8456. https://doi.org/10.3390/ijms22168456

AMA Style

Rohaim MA, Al-Natour MQ, Abdelsabour MA, El Naggar RF, Madbouly YM, Ahmed KA, Munir M. Transgenic Chicks Expressing Interferon-Inducible Transmembrane Protein 1 (IFITM1) Restrict Highly Pathogenic H5N1 Influenza Viruses. International Journal of Molecular Sciences. 2021; 22(16):8456. https://doi.org/10.3390/ijms22168456

Chicago/Turabian Style

Rohaim, Mohammed A., Mohammad Q. Al-Natour, Mohammed A. Abdelsabour, Rania F. El Naggar, Yahia M. Madbouly, Kawkab A. Ahmed, and Muhammad Munir. 2021. "Transgenic Chicks Expressing Interferon-Inducible Transmembrane Protein 1 (IFITM1) Restrict Highly Pathogenic H5N1 Influenza Viruses" International Journal of Molecular Sciences 22, no. 16: 8456. https://doi.org/10.3390/ijms22168456

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