Idoko-Akoh A, Goldhill DH, Sheppard CM, Bialy D, Q. Creating resistance to avian influenza infection through genome editing of the ANP32 gene family. Nat Commun. 2023 Oct 10;14(1):6136
Chickens genetically resistant to avian influenza could prevent future outbreaks. In chickens, influenza A virus (IAV) relies on host protein ANP32A. Here we use CRISPR/Cas9 to generate homozygous gene edited (GE) chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction. After IAV challenge, 9/10 edited chickens remain uninfected. Challenge with a higher dose, however, led to breakthrough infections. Breakthrough IAV virus contained IAV polymerase gene mutations that conferred adaptation to the edited chicken ANP32A. Unexpectedly, this virus also replicated in chicken embryos edited to remove the entire ANP32A gene and instead co-opted alternative ANP32 protein family members, chicken ANP32B and ANP32E. Additional genome editing for removal of ANP32B and ANP32E eliminated all viral growth in chicken cells. Our data illustrate a first proof of concept step to generate IAV-resistant chickens and show that multiple genetic modifications will be required to curtail viral escape.
See Also:
Latest articles in those days:
- Nucleic acid detection and genomic sequence analysis of one H5N1 avian influenza virus from wide birds around Qinghai Lake 12 hours ago
- An aggregated dataset of serial morbidity and titer measurements from influenza A virus-infected ferrets 16 hours ago
- Structures of H5N1 influenza polymerase with ANP32B reveal mechanisms of genome replication and host adaptation 3 days ago
- Risk assessment of a highly pathogenic H5N1 influenza virus from mink 3 days ago
- Detection of clade 2.3.4.4b highly pathogenic H5N1 influenza virus in New York City 3 days ago
[Go Top] [Close Window]