OMIA 001299-9031 : Resistance to avian sarcoma and leukosis viruses, subgroup A in Gallus gallus

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2004

Species-specific symbol: tva

Species-specific description: As in many other cases of single-locus resistance, resistance to type A avian leukosis viruses is due to the lack of a functional receptor for the viruses.

Inheritance: Resistance to the A subgroup of avian sarcoma and leukosis viruses is a single-locus trait, with susceptibility being dominant and resistance recessive (Crittenden et al. 1967), who named the locus "tumour virus a" (tva).

Mapping: Bates et al. (1998) reported that the tva gene maps to within 5 cM of the receptor gene identified by Young et al. (1993), which (given the limited power of the linkage analysis) was strong evidence that the two genes are one in the same.

Markers: y

Molecular basis: The tva gene (i.e. the gene encoding the receptor for subgroup A viruses) was isolated, cloned and partially sequenced by Young et al. (1993), who performed two rounds of transfection with chicken genomic DNA (first into a monkey cell line and then into a mouse cell line) and subsequent selection for clones that are susceptible to subgroup A virus (and hence must be expressing the receptor for subgroup A viruses).

Elleder et al. (2004) fully sequenced this gene, and reported that two "different defects were identified in cDNAs cloned from two different ASLV(A)-resistant inbred chickens, line C and line 7(2). Line C tva(r) contains a single base pair substitution, resulting in a cysteine-to-tryptophan change in the LDLR-like region of Tva. This mutation [called allele tva^1] drastically reduces the binding affinity of Tva(R) for the ASLV(A) envelope glycoproteins. Line 7(2) tva(r2) contains a 4-bp insertion in exon 1 that causes a change in the reading frame, which blocks expression of the Tva receptor." This allele is called tva^r2.

Reinišová et al. (2012) identified two more resistance alleles at this locus, both disrupting splicing: tva^r3 is a 10bp deletion in intron 1 that includes a critical nucleotide of the deduced branch-point signal; tva^r4 is a 5bp deletion which also destroys the branch point signal.

Chen et al. (2015) identified two more resistance alleles, namely tva^r5 ("a [10bp] deletion of the sequence CGCTCACCCC (nucleotides 502 to 511)") and tva^r6 ("a [15bp] deletion of the sequence CGCTCACCCCGCCCC (nucleotides 502 to 516)").

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CD320 CD320 molecule Gallus gallus 28 NC_006115.5 (985447..988950) CD320 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Resistance to avian sarcoma and leukosis viruses, subgroup A CD320 missense c.120C>G p.C40W 2004 15564460
Resistance to avian sarcoma and leukosis viruses, subgroup A CD320 tva^r2 insertion, small (<=20) c.48insCTCG 2004 15564460
Resistance to avian sarcoma and leukosis viruses, subgroup A CD320 deletion, small (<=20) c.502_511delCGCTCACCCC 2015 25873518
Resistance to avian sarcoma and leukosis viruses, subgroup A CD320 deletion, small (<=20) c.502_516delCGCTCACCCCGCCCC 2015 25873518
Resistance to avian sarcoma and leukosis viruses, subgroup A CD320 splicing c.506-515del10 2012 22171251
Resistance to avian sarcoma and leukosis viruses, subgroup A CD320 splicing c.507-511del5 2012 22171251

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2015 Chen, W., Liu, Y., Li, H., Chang, S., Shu, D., Zhang, H., Chen, F., Xie, Q. :
Intronic deletions of tva receptor gene decrease the susceptibility to infection by avian sarcoma and leukosis virus subgroup A. Sci Rep 5:9900, 2015. Pubmed reference: 25873518. DOI: 10.1038/srep09900.
2012 Reinišová, M., Plachý, J., Trejbalová, K., Šenigl, F., Kučerová, D., Geryk, J., Svoboda, J., Hejnar, J. :
Intronic deletions that disrupt mRNA splicing of the tva receptor gene result in decreased susceptibility to infection by avian sarcoma and leukosis virus subgroup A. J Virol 86:2021-30, 2012. Pubmed reference: 22171251. DOI: 10.1128/JVI.05771-11.
2011 Beier, K.T., Samson, M.E., Matsuda, T., Cepko, C.L. :
Conditional expression of the TVA receptor allows clonal analysis of descendents from Cre-expressing progenitor cells. Dev Biol 353:309-20, 2011. Pubmed reference: 21397594. DOI: 10.1016/j.ydbio.2011.03.004.
2006 Contreras-Alcantara, S., Godby, J.A., Delos, S.E. :
The single ligand-binding repeat of Tva, a low density lipoprotein receptor-related protein, contains two ligand-binding surfaces. J Biol Chem 281:22827-38, 2006. Pubmed reference: 16769730. DOI: 10.1074/jbc.M512599200.
2005 Rai, T., Caffrey, M., Rong, L. :
Identification of two residues within the LDL-A module of Tva that dictate the altered receptor specificity of mutant subgroup A avian sarcoma and leukosis viruses. J Virol 79:14962-6, 2005. Pubmed reference: 16282495. DOI: 10.1128/JVI.79.23.14962-14966.2005.
2004 Elleder, D., Melder, D.C., Trejbalova, K., Svoboda, J., Federspiel, M.J. :
Two different molecular defects in the Tva receptor gene explain the resistance of two tvar lines of chickens to infection by subgroup A avian sarcoma and leukosis viruses. J Virol 78:13489-500, 2004. Pubmed reference: 15564460. DOI: 10.1128/JVI.78.24.13489-13500.2004.
Elleder, D., Plachý, J., Hejnar, J., Geryk, J., Svoboda, J. :
Close linkage of genes encoding receptors for subgroups A and C of avian sarcoma/leucosis virus on chicken chromosome 28. Anim Genet 35:176-81, 2004. Pubmed reference: 15147387. DOI: 10.1111/j.1365-2052.2004.01118.x.
Kvaratskhelia, M., Clark, P.K., Hess, S., Melder, D.C., Federspiel, M.J., Hughes, S.H. :
Identification of glycosylation sites in the SU component of the Avian Sarcoma/Leukosis virus Envelope Glycoprotein (Subgroup A) by mass spectrometry. Virology 326:171-81, 2004. Pubmed reference: 15262505. DOI: 10.1016/j.virol.2004.05.020.
Rai, T., Marble, D., Rihani, K., Rong, L. :
The spacing between cysteines two and three of the LDL-A module of Tva is important for subgroup A avian sarcoma and leukosis virus entry. J Virol 78:683-91, 2004. Pubmed reference: 14694099.
2003 Yu, X., Wang, Q.Y., Guo, Y., Dolmer, K., Young, J.A., Gettins, P.G., Rong, L. :
Kinetic analysis of binding interaction between the subgroup A Rous sarcoma virus glycoprotein SU and its cognate receptor Tva: calcium is not required for ligand binding. J Virol 77:7517-26, 2003. Pubmed reference: 12805452.
2002 Delos, S.E., Burdick, M.J., White, J.M. :
A single glycosylation site within the receptor-binding domain of the avian sarcoma/leukosis virus glycoprotein is critical for receptor binding. Virology 294:354-63, 2002. Pubmed reference: 12009877. DOI: 10.1006/viro.2001.1339.
Wang, Q.Y., Huang, W., Dolmer, K., Gettins, P.G., Rong, L. :
Solution structure of the viral receptor domain of Tva and its implications in viral entry. J Virol 76:2848-56, 2002. Pubmed reference: 11861852.
Wang, Q.Y., Manicassamy, B., Yu, X., Dolmer, K., Gettins, P.G., Rong, L. :
Characterization of the LDL-A module mutants of Tva, the subgroup A Rous sarcoma virus receptor, and the implications in protein folding. Protein Sci 11:2596-605, 2002. Pubmed reference: 12381843. DOI: 10.1110/ps.0219802.
2001 Tonelli, M., Peters, R.J., James, T.L., Agard, D.A. :
The solution structure of the viral binding domain of Tva, the cellular receptor for subgroup A avian leukosis and sarcoma virus. FEBS Lett 509:161-8, 2001. Pubmed reference: 11768384.
Wang, Q.Y., Dolmer, K., Huang, W., Gettins, P.G., Rong, L. :
Role of calcium in protein folding and function of Tva, the receptor of subgroup A avian sarcoma and leukosis virus. J Virol 75:2051-8, 2001. Pubmed reference: 11160709. DOI: 10.1128/JVI.75.5.2051-2058.2001.
1999 Balliet, J.W., Berson, J., D'Cruz, C.M., Huang, J., Crane, J., Gilbert, J.M., Bates, P. :
Production and characterization of a soluble, active form of Tva, the subgroup A avian sarcoma and leukosis virus receptor. J Virol 73:3054-61, 1999. Pubmed reference: 10074155.
1998 Bates, P., Rong, L.J., Varmus, H.E., Young, J.A.T., Crittenden, L.B. :
Genetic mapping of the cloned subgroup a avian sarcoma and leukosis virus receptor gene to the tva locus Journal of Virology 72:2505-2508, 1998. Pubmed reference: 9499114.
Rong, L., Gendron, K., Strohl, B., Shenoy, R., Wool-Lewis, R.J., Bates, P. :
Characterization of determinants for envelope binding and infection in tva, the subgroup A avian sarcoma and leukosis virus receptor. J Virol 72:4552-9, 1998. Pubmed reference: 9573218.
1997 Mehta, S.C., Pani, P.K. :
Interrelationship between tumour virus receptors, A and C, coded by host cell genes in fowl. Indian J Exp Biol 35:33-6, 1997. Pubmed reference: 9279130.
1996 Zingler, K., Young, J.A. :
Residue Trp-48 of Tva is critical for viral entry but not for high-affinity binding to the SU glycoprotein of subgroup A avian leukosis and sarcoma viruses. J Virol 70:7510-6, 1996. Pubmed reference: 8892869.
1995 Rong, L., Bates, P. :
Analysis of the subgroup A avian sarcoma and leukosis virus receptor: the 40-residue, cysteine-rich, low-density lipoprotein receptor repeat motif of Tva is sufficient to mediate viral entry. J Virol 69:4847-53, 1995. Pubmed reference: 7609052.
1994 Gilbert, J.M., Bates, P., Varmus, H.E., White, J.M. :
The receptor for the subgroup A avian leukosis-sarcoma viruses binds to subgroup A but not to subgroup C envelope glycoprotein. J Virol 68:5623-8, 1994. Pubmed reference: 8057442.
1993 Bates, P., Young, J.A., Varmus, H.E. :
A receptor for subgroup A Rous sarcoma virus is related to the low density lipoprotein receptor. Cell 74:1043-51, 1993. Pubmed reference: 8402880.
Young, J.A., Bates, P., Varmus, H.E. :
Isolation of a chicken gene that confers susceptibility to infection by subgroup A avian leukosis and sarcoma viruses. J Virol 67:1811-6, 1993. Pubmed reference: 8383211.
1991 Pani, P.K., Naithani, S. :
Genetics of post-hatching survival potential of Australorp chicks infected as embryos by subgroup A Rous sarcoma virus: further support to 4-allele genetic model. Indian J Exp Biol 29:416-21, 1991. Pubmed reference: 1655642.
1977 Dren, C.N., Pani, P.K. :
Genetic control of resistance to subgroup A and subgroup C tumour viruses in Rhode Island Red fowl: evidence for linkage between the tumour virus a (tva) and tumour virus c (tvc) loci. J Gen Virol 35:13-23, 1977. Pubmed reference: 192840.
1974 Pani, P.K. :
Close linkage between genetic loci controlling response of fowl to subgroup A and subgroup C sarcoma viruses. J Gen Virol 22:187-95, 1974. Pubmed reference: 4362402.
1971 Payne, L.N., Pani, P.K. :
Evidence for linkage between genetic loci controlling response of fowl to subgroup A and subgroup C sarcoma viruses. J Gen Virol 13:253-9, 1971. Pubmed reference: 4333713.
1967 Crittenden, L.B., Stone, H.A., Reamer, R.H., Okazaki, W. :
Two loci controlling genetic cellular resistance to avian leukosis-sarcoma viruses. J Virol 1:898-904, 1967. Pubmed reference: 4316238.

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