Delayed nuclear localization of CRISPR/Cas9-modified fiber of Fowl adenovirus serotype 8b reduced pathogenicity in Specific pathogen-free Chicken embryonic liver cells

Ahmed S 1 , Azli B 2 , Razak MA 3 , Hair-Bejo M 4 , Omar AR 5 , Ideris A 6 Show all authors , Isa NM 7

Affiliations 

  • 1 Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia; Department of Science Laboratory Technology, Jigawa State Polytechnic, 7040 Dutse, Jigawa state, Nigeria. Electronic address: Sahmed@jippoly.edu.ng
  • 2 Laboratory of Vaccine and Biomolecules, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia. Electronic address: bahiyahazli@gmail.com
  • 3 Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia; Laboratory of Vaccine and Biomolecules, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia. Electronic address: mariatulqabtiah@upm.edu.my
  • 4 Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia; Laboratory of Vaccine and Biomolecules, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia. Electronic address: hairbejo@upm.edu.my
  • 5 Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia; Laboratory of Vaccine and Biomolecules, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia. Electronic address: aro@upm.edu.my
  • 6 Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia; Laboratory of Vaccine and Biomolecules, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia. Electronic address: aiini@upm.edu.my
  • 7 Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia; Laboratory of Vaccine and Biomolecules, Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400 Selangor, Malaysia. Electronic address: nurulfiza@upm.edu.my
Microb Pathog, 2025 Mar 15.
PMID: 40097027 DOI: 10.1016/j.micpath.2025.107482

Abstract

Fowl adenovirus (FAdV) poses incessant outbreaks to poultry production worldwide, and Inclusion body hepatitis (IBH) is a predominant FAdV infectious disease. Currently, limited vaccines are available in Malaysia to fight against the local predominant FAdV strain 8b isolate (FAdV-8b), posing a desperate demand for efficient vaccine development. The fiber protein of FAdV is one of the major constituents of the adenoviral capsid involved in the virulence of pathogens. Hence, the aim was to modify the fiber gene of FAdV-8b UPMT27 to develop a live attenuated FAdV vaccine via the gene-editing CRISPR/Cas9 technology. Primary specific pathogen-free (SPF) chicken embryonic liver cells (CELs) infected with the modified isolated (cfUPMT27) were reported with significantly reduced cytopathic effects, delayed viral localization into the nucleus, and low apoptotic rates. cfUPMT27 isolate also exhibited constant amino acid substitution of Y179D in subsequent passages. Meanwhile, the liver of cfUPMT27 inoculated-SPF chicken embryonic eggs (CEE) was observed with mild hydropericardium and reported with a delayed mortality at 6-days post-infection (dpi). This holistic, integrative study incorporating genetic, pathology, and immunology analysis proposed cfUPMT27 isolate as a candidate vaccine for FAdV infections, providing efficient future protection in chickens.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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