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Genetic Resistance to Avian Leukosis Viruses Induced by CRISPR/Cas9 Editing of Specific Receptor Genes in Chicken Cells
A. Koslová, D. Kučerová, M. Reinišová, J. Geryk, P. Trefil, J. Hejnar,
Language English Country Switzerland
Document type Journal Article, Research Support, Non-U.S. Gov't
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PubMed
30400152
DOI
10.3390/v10110605
Knihovny.cz E-resources
- MeSH
- Cell Line MeSH
- CRISPR-Cas Systems * MeSH
- Gene Editing * MeSH
- Genetic Techniques MeSH
- Genetic Vectors genetics MeSH
- RNA, Guide, Kinetoplastida MeSH
- Chickens MeSH
- Disease Resistance genetics MeSH
- Avian Leukosis genetics virology MeSH
- Base Sequence MeSH
- Genes, Viral MeSH
- Receptors, Virus genetics metabolism MeSH
- Avian Leukosis Virus physiology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Avian leukosis viruses (ALVs), which are pathogens of concern in domestic poultry, utilize specific receptor proteins for cell entry that are both necessary and sufficient for host susceptibility to a given ALV subgroup. This unequivocal relationship offers receptors as suitable targets of selection and biotechnological manipulation with the aim of obtaining virus-resistant poultry. This approach is further supported by the existence of natural knock-outs of receptor genes that segregate in inbred lines of chickens. We used CRISPR/Cas9 genome editing tools to introduce frame-shifting indel mutations into tva, tvc, and tvj loci encoding receptors for the A, C, and J ALV subgroups, respectively. For all three loci, the homozygous frame-shifting indels generating premature stop codons induced phenotypes which were fully resistant to the virus of respective subgroup. In the tvj locus, we also obtained in-frame deletions corroborating the importance of W38 and the four amino-acids preceding it. We demonstrate that CRISPR/Cas9-mediated knock-out or the fine editing of ALV receptor genes might be the first step in the development of virus-resistant chickens.
BIOPHARM Research Institute of Biopharmacy and Veterinary Drugs 254 49 Jílové u Prahy Czech Republic
References provided by Crossref.org
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