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 B12 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.
- MeSH
- Gene Editing MeSH
- Gene Knockout Techniques MeSH
- Chickens virology MeSH
- Chick Embryo MeSH
- Methylmalonic Acid blood MeSH
- Frameshift Mutation MeSH
- Avian Proteins genetics physiology MeSH
- Receptors, Virus genetics physiology MeSH
- Avian Leukosis Virus classification physiology MeSH
- Vitamin B 12 metabolism MeSH
- Animals MeSH
- Check Tag
- Chick Embryo MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
... antigens. 29 -- 1 -22 Inherited and acquired defects in the immune system result in increased susceptibility ... ... Fee receptor. 436 -- 10- 25 IgE-mediated activation of accessory cells has an important role in resistance ... ... immunity wanes. 571 -- Summary. 573 -- Acquired immune deficiency syndrome. 573 -- 13-25 HIV is a retrovirus ... ... the course of infection HIV accumulates many mutations, which can result in the outgrowth of drug-resistant ... ... of IgE-mediated allergic disease. 607 -- 14-4 Environmental factors may interact with genetic susceptibility ...
9th edition xx, 904 stran : ilustrace, tabulky ; 28 cm
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- alergologie a imunologie
- biologie
- fyziologie
- NML Publication type
- kolektivní monografie
... molecules. 29 -- 1-21 Inherited and acquired defects in the immune system result in increased susceptibility ... ... Fee receptor. 421 -- 10-25 IgE-mediated activation of accessory cells has an important role in resistance ... ... viruses persist in vivo by ceasing to replicate until immunity wanes. 512 -- 13-3 Some pathogens resist ... ... 543 -- 13-24 Most individuals infected with HIV progress over time to AIDS. 545 -- 13-25 HIV is a retrovirus ... ... rate of progression of disease. 549 -- 13-27 A genetic deficiency of the co-receptor CCR5 confers resistance ...
8th ed. xix, 868 s. : il., tab.
- MeSH
- Immunity MeSH
- Immune System MeSH
- Immunotherapy MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- alergologie a imunologie
- biologie
The group of closely related avian sarcoma and leukosis viruses (ASLVs) evolved from a common ancestor into multiple subgroups, A to J, with differential host range among galliform species and chicken lines. These subgroups differ in variable parts of their envelope glycoproteins, the major determinants of virus interaction with specific receptor molecules. Three genetic loci, tva, tvb, and tvc, code for single membrane-spanning receptors from diverse protein families that confer susceptibility to the ASLV subgroups. The host range expansion of the ancestral virus might have been driven by gradual evolution of resistance in host cells, and the resistance alleles in all three receptor loci have been identified. Here, we characterized two alleles of the tva receptor gene with similar intronic deletions comprising the deduced branch-point signal within the first intron and leading to inefficient splicing of tva mRNA. As a result, we observed decreased susceptibility to subgroup A ASLV in vitro and in vivo. These alleles were independently found in a close-bred line of domestic chicken and Indian red jungle fowl (Gallus gallus murghi), suggesting that their prevalence might be much wider in outbred chicken breeds. We identified defective splicing to be a mechanism of resistance to ASLV and conclude that such a type of mutation could play an important role in virus-host coevolution.
- MeSH
- Alpharetrovirus genetics physiology MeSH
- Genetic Predisposition to Disease MeSH
- Introns MeSH
- Chickens genetics metabolism virology MeSH
- Molecular Sequence Data MeSH
- Poultry Diseases genetics metabolism virology MeSH
- Avian Proteins genetics metabolism MeSH
- Sarcoma, Avian genetics metabolism virology MeSH
- Amino Acid Sequence MeSH
- Base Sequence MeSH
- Sequence Deletion MeSH
- RNA Splicing MeSH
- Receptors, Virus genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The avian sarcoma and leukosis virus (ASLV) family of retroviruses contains five highly related envelope subgroups (A to E) thought to have evolved from a common viral ancestor in the chicken population. Three genetic loci in chickens determine the susceptibility or resistance of cells to infection by the subgroup A to E ASLVs. Some inbred lines of chickens display phenotypes that are somewhere in between either efficiently susceptible or resistant to infection by specific subgroups of ASLV. The tvb gene encodes the receptor for subgroups B, D, and E ASLVs. The wild-type Tvb(S1) receptor confers susceptibility to subgroups B, D, and E ASLVs. In this study, the genetic defect that accounts for the altered susceptibility of an inbred chicken line, line M, to infection by ASLV(B), ASLV(D), and ASLV(E) was identified. The tvb gene in line M, tvb(r2), encodes a mutant Tvb(S1) receptor protein with a substitution of a serine for a cysteine at position 125 (C125S). Here, we show that the C125S substitution in Tvb(S1) significantly reduces the susceptibility of line M cells to infection by ASLV(B) and ASLV(D) and virtually eliminates susceptibility to ASLV(E) infection both in cultured cells and in the incidence and growth of avian sarcoma virus-induced sarcomas in chickens. The C125S substitution significantly reduces the binding affinity of the Tvb(S1) receptor for the subgroup B, D, and E ASLV envelope glycoproteins. These are the first results that demonstrate a possible role of the cysteine-rich domain 3 in the function of the Tvb receptors.
- MeSH
- Alleles MeSH
- Alpharetrovirus classification pathogenicity MeSH
- DNA Primers MeSH
- Species Specificity MeSH
- Financing, Organized MeSH
- Membrane Fusion MeSH
- Genetic Predisposition to Disease MeSH
- Tumor Virus Infections virology MeSH
- Cells, Cultured MeSH
- Chick Embryo MeSH
- Molecular Sequence Data MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Flow Cytometry MeSH
- Retroviridae Infections virology MeSH
- Amino Acid Sequence MeSH
- Base Sequence MeSH
- Sequence Homology, Amino Acid MeSH
- Amino Acid Substitution MeSH
- Receptors, Virus physiology genetics chemistry MeSH
- Animals MeSH
- Check Tag
- Chick Embryo MeSH
- Animals MeSH
... Bardata 45 -- Sulphation of industrial and other chemicals in man: susceptibility to chemical induced ... ... and circumventing the emergence of resistant virus strains, J. ... ... : role of the ternary DNA complex in drug sensitivity and resistance, L.M. ... ... Mullins 390 -- Application of novel in vitro technology to human resistance artery disease, M.J. ... ... A resource to identity genes involved in malignancy and in disease susceptibility, N.K. ...
Biomedical and health research, ISSN 0929-6743 vol. 9
xxxix, 744 s. ; 24 cm
- Conspectus
- Veřejné zdraví a hygiena
- NML Fields
- veřejné zdravotnictví
- politologie, politika, zdravotní politika
... Develop from Vegetative Cells when They Face Starvation 84 -- Endospores Have Unusual Staining and Resistance ... ... Unrelated Bacteria 175 -- Restriction and Modification of DNA 175 -- Modification Enzymes Confer Resistance ... ... of People to Certain Infections 353 Age and Stress Are Also Factors that Determine Susceptibility to ... ... Review Questions 527 Food Poisoning 528 -- Staphylococcal Food Poisoning Is the Result of a Heat-resistant ... ... Can Be Quantified by Determining Minimal Inhibitory Concentrations 655 The Terms Sensitive and Resistant ...
XXVIII, 812 s. : il. ; 32 cm
sv.
- MeSH
- Allergy and Immunology MeSH
- Microbiology MeSH
- Publication type
- Collected Work MeSH
- Conspectus
- Mikrobiologie
- NML Fields
- alergologie a imunologie
- mikrobiologie, lékařská mikrobiologie
