Knock-Out of Retrovirus Receptor Gene <i>Tva</i> in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B<sub>12</sub>)-Dependent Level of Methylmalonic Acid
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 intro...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/13/12/2504 |
| _version_ | 1797499932588900352 |
|---|---|
| author | Anna Koslová Pavel Trefil Jitka Mucksová Veronika Krchlíková Jiří Plachý Jakub Krijt Markéta Reinišová Dana Kučerová Josef Geryk Jiří Kalina Filip Šenigl Daniel Elleder Viktor Kožich Jiří Hejnar |
| author_facet | Anna Koslová Pavel Trefil Jitka Mucksová Veronika Krchlíková Jiří Plachý Jakub Krijt Markéta Reinišová Dana Kučerová Josef Geryk Jiří Kalina Filip Šenigl Daniel Elleder Viktor Kožich Jiří Hejnar |
| author_sort | Anna Koslová |
| collection | DOAJ |
| description | 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 <i>tva</i> locus with the aim of knocking-out Tva expression and creating a virus-resistant chicken line. The <i>tva</i> 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 <i>tva</i> −/− 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 <i>tva</i> +/+ and <i>tva</i> +/− siblings. We also found a specific disorder of the cobalamin/vitamin B<sub>12</sub> 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. |
| first_indexed | 2024-03-10T03:54:34Z |
| format | Article |
| id | doaj.art-dfebb64862e64b58b3293fd1b2c3fcfe |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T03:54:34Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-dfebb64862e64b58b3293fd1b2c3fcfe2023-11-23T10:58:52ZengMDPI AGViruses1999-49152021-12-011312250410.3390/v13122504Knock-Out of Retrovirus Receptor Gene <i>Tva</i> in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B<sub>12</sub>)-Dependent Level of Methylmalonic AcidAnna Koslová0Pavel Trefil1Jitka Mucksová2Veronika Krchlíková3Jiří Plachý4Jakub Krijt5Markéta Reinišová6Dana Kučerová7Josef Geryk8Jiří Kalina9Filip Šenigl10Daniel Elleder11Viktor Kožich12Jiří Hejnar13Institute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicBIOPHARM, Research Institute of Biopharmacy and Veterinary Drugs, Pohoří-Chotouň 90, 254 49 Jílové u Prahy, Czech RepublicBIOPHARM, Research Institute of Biopharmacy and Veterinary Drugs, Pohoří-Chotouň 90, 254 49 Jílové u Prahy, Czech RepublicInstitute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicDepartment of Pediatrics and Inherited Metabolic Disorders, Charles University, First Faculty of Medicine and General University Hospital in Prague, 128 08 Prague, Czech RepublicInstitute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicBIOPHARM, Research Institute of Biopharmacy and Veterinary Drugs, Pohoří-Chotouň 90, 254 49 Jílové u Prahy, Czech RepublicInstitute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicInstitute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicDepartment of Pediatrics and Inherited Metabolic Disorders, Charles University, First Faculty of Medicine and General University Hospital in Prague, 128 08 Prague, Czech RepublicInstitute of Molecular Genetics, Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech RepublicThe 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 <i>tva</i> locus with the aim of knocking-out Tva expression and creating a virus-resistant chicken line. The <i>tva</i> 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 <i>tva</i> −/− 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 <i>tva</i> +/+ and <i>tva</i> +/− siblings. We also found a specific disorder of the cobalamin/vitamin B<sub>12</sub> 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.https://www.mdpi.com/1999-4915/13/12/2504avian leukosis virus subgroups A/K<i>tva</i>gene editing in chickenvitamin B<sub>12</sub>/cobalamin |
| spellingShingle | Anna Koslová Pavel Trefil Jitka Mucksová Veronika Krchlíková Jiří Plachý Jakub Krijt Markéta Reinišová Dana Kučerová Josef Geryk Jiří Kalina Filip Šenigl Daniel Elleder Viktor Kožich Jiří Hejnar Knock-Out of Retrovirus Receptor Gene <i>Tva</i> in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B<sub>12</sub>)-Dependent Level of Methylmalonic Acid Viruses avian leukosis virus subgroups A/K <i>tva</i> gene editing in chicken vitamin B<sub>12</sub>/cobalamin |
| title | Knock-Out of Retrovirus Receptor Gene <i>Tva</i> in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B<sub>12</sub>)-Dependent Level of Methylmalonic Acid |
| title_full | Knock-Out of Retrovirus Receptor Gene <i>Tva</i> in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B<sub>12</sub>)-Dependent Level of Methylmalonic Acid |
| title_fullStr | Knock-Out of Retrovirus Receptor Gene <i>Tva</i> in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B<sub>12</sub>)-Dependent Level of Methylmalonic Acid |
| title_full_unstemmed | Knock-Out of Retrovirus Receptor Gene <i>Tva</i> in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B<sub>12</sub>)-Dependent Level of Methylmalonic Acid |
| title_short | Knock-Out of Retrovirus Receptor Gene <i>Tva</i> in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B<sub>12</sub>)-Dependent Level of Methylmalonic Acid |
| title_sort | knock out of retrovirus receptor gene i tva i in the chicken confers resistance to avian leukosis virus subgroups a and k and affects cobalamin vitamin b sub 12 sub dependent level of methylmalonic acid |
| topic | avian leukosis virus subgroups A/K <i>tva</i> gene editing in chicken vitamin B<sub>12</sub>/cobalamin |
| url | https://www.mdpi.com/1999-4915/13/12/2504 |
| work_keys_str_mv | AT annakoslova knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT paveltrefil knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT jitkamucksova knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT veronikakrchlikova knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT jiriplachy knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT jakubkrijt knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT marketareinisova knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT danakucerova knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT josefgeryk knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT jirikalina knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT filipsenigl knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT danielelleder knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT viktorkozich knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid AT jirihejnar knockoutofretrovirusreceptorgeneitvaiinthechickenconfersresistancetoavianleukosisvirussubgroupsaandkandaffectscobalaminvitaminbsub12subdependentlevelofmethylmalonicacid |