Knock-Out of Retrovirus Receptor Gene Tva in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B-12)-Dependent Level of Methylmalonic Acid

0554917 - ÚMG 2022 RIV CH eng J - Článek v odborném periodiku
Koslová, Anna - Trefil, P. - Mucksová, J. - Krchlíková, Veronika - Plachý, Jiří - Krijt, J. - Reinišová, Markéta - Kučerová, Dana - Geryk, Josef - Kalina, J. - Šenigl, Filip - Elleder, Daniel - Kožich, V. - Hejnar, Jiří
Knock-Out of Retrovirus Receptor Gene Tva in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B-12)-Dependent Level of Methylmalonic Acid.
Viruses. Roč. 13, č. 12 (2021), č. článku 2504. E-ISSN 1999-4915
Grant CEP: GA MZe(CZ) QK1810344
Institucionální podpora: RVO:68378050
Klíčová slova: avian leukosis virus subgroups A * k * tva * gene editing in chicken * vitamin B-12 * cobalamin
Obor OECD: Virology
Impakt faktor: 5.818, rok: 2021
Způsob publikování: Open access
https://www.mdpi.com/1999-4915/13/12/2504

The chicken Tva cell surface protein, a member of the low-density lipoprotein receptor family, has been identified as an entry receptor for avian leukosis virus of classic subgroup A and newly emerging subgroup K. Because both viruses represent an important concern for the poultry industry, we introduced a frame-shifting deletion into the chicken tva locus with the aim of knocking-out Tva expression and creating a virus-resistant chicken line. The tva knock-out was prepared by CRISPR/Cas9 gene editing in chicken primordial germ cells and orthotopic transplantation of edited cells into the testes of sterilized recipient roosters. The resulting tva/- chickens tested fully resistant to avian leukosis virus subgroups A and K, both in in vitro and in vivo assays, in contrast to their susceptible tva +/+ and tva +/- siblings. We also found a specific disorder of the cobalamin/vitamin B-12 metabolism in the tva knock-out chickens, which is in accordance with the recently recognized physiological function of Tva as a receptor for cobalamin in complex with transcobalamin transporter. Last but not least, we bring a new example of the de novo resistance created by CRISPR/Cas9 editing of pathogen dependence genes in farm animals and, furthermore, a new example of gene editing in chicken.
Trvalý link: http://hdl.handle.net/11104/0329536