Avian sarcoma/leukosis virus (RCAS)-mediated over-expression of IFITM3 protects chicks from highly pathogenic avian influenza virus subtype H5N1

Mohammed A Rohaim; Emma Louise Gardiner; Rania F El Naggar; Mohammed A Abdelsabour; Yahia M Madbouly; Mustafa O Atasoy; Kawkab A Ahmed; Munir M El-Safty; Muhammad Munir

doi:10.1016/j.micinf.2023.105231

Avian sarcoma/leukosis virus (RCAS)-mediated over-expression of IFITM3 protects chicks from highly pathogenic avian influenza virus subtype H5N1

Microbes Infect. 2024 Jan-Feb;26(1-2):105231. doi: 10.1016/j.micinf.2023.105231. Epub 2023 Sep 28.

Authors

Mohammed A Rohaim¹, Emma Louise Gardiner², Rania F El Naggar³, Mohammed A Abdelsabour⁴, Yahia M Madbouly⁴, Mustafa O Atasoy², Kawkab A Ahmed⁵, Munir M El-Safty⁶, Muhammad Munir⁷

Affiliations

¹ Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YG, UK; Department of Virology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
² Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YG, UK.
³ Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YG, UK; Department of Virology, Faculty of Veterinary Medicine, University of Sadat City, Sadat 32897, Egypt.
⁴ Department of Poultry Viral Vaccines, Veterinary Serum and Vaccine Research Institute (VSVRI), Agriculture Research Centre (ARC), Cairo 11435, Egypt.
⁵ Central Laboratory for Evaluation of Veterinary Biologics, Abbasia, Cairo, 11381, Egypt.
⁶ Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
⁷ Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YG, UK. Electronic address: muhammad.munir@lancaster.ac.uk.

PMID: 37777054
DOI: 10.1016/j.micinf.2023.105231

Abstract

Broad-spectrum antiviral activities of interferon-induced transmembrane proteins (IFITMs) are primarily attributed to in vitro inhibition of viral entry. Here, we used an avian sarcoma-leukosis virus (RCAS)-based gene transfer system and successfully generated chicks that constitutively express chicken IFITM3 (chIFITM3). The chIFITM3-overexpressing chicks showed significant protection and disease tolerance against highly pathogenic avian influenza virus (HPAIV) H5N1 (Clade 2.2.1.2). The chicks, overexpressing chIFITM3, also showed delayed onset of clinical symptoms, reduced viral shedding, and alleviated histopathologic alterations compared to control and challenged chicks. These findings highlight that overexpression of chIFITM3 provide a substantial defense against zoonotic H5N1 in vivo.

Keywords: Chicken; H5N1; IFITM3; ISG; Influenza.

MeSH terms

Animals
Chickens
Influenza A Virus, H5N1 Subtype* / genetics
Influenza A virus*
Influenza in Birds* / prevention & control
Sarcoma, Avian*