Genetic Resistance to Avian Leukosis Viruses Induced by CRISPR/Cas9 Editing of Specific Receptor Genes in Chicken Cells

0500360 - ÚMG 2019 RIV CH eng J - Článek v odborném periodiku
Koslová, Anna - Kučerová, Dana - Reinišová, Markéta - Geryk, Josef - Trefil, P. - Hejnar, Jiří
Genetic Resistance to Avian Leukosis Viruses Induced by CRISPR/Cas9 Editing of Specific Receptor Genes in Chicken Cells.
Viruses. Roč. 10, č. 11 (2018), č. článku 605. E-ISSN 1999-4915
Grant CEP: GA ČR GA15-24776S; GA MŠMT LO1419
Institucionální podpora: RVO:68378050
Klíčová slova: avian leukosis virus * retrovirus receptor * virus-resistance in chicken * CRISPR /Cas9
Obor OECD: Virology
Impakt faktor: 3.811, rok: 2018

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.
Trvalý link: http://hdl.handle.net/11104/0292444