Two Different Molecular Defects in the Tva Receptor Gene Explain the Resistance of Two tva super(r) Lines of Chickens to Infection by Subgroup A Avian Sarcoma and Leukosis Viruses

• Published in: Journal of virology 2004-12, Vol.78 (24), p.13489-13500
• Main Authors: Elleder, Daniel, Melder, Deborah C, Trejbalova, Katerina, Svoboda, Jan, Federspiel, Mark J
• Format: Article
• Language: English
• Subjects: Avian sarcoma and leukosis virus
• ISSN: 0022-538X

The subgroup A to E avian sarcoma and leukosis viruses (ASLVs) are highly related and are thought to have evolved from a common ancestor. These viruses use distinct cell surface proteins as receptors to gain entry into avian cells. Chickens have evolved resistance to infection by the ASLVs. We have identified the mutations responsible for the block to virus entry in chicken lines resistant to infection by subgroup A ASLVs [ASLV(A)]. The tva genetic locus determines the susceptibility of chicken cells to ASLV(A) viruses. In quail, the ASLV(A) susceptibility allele tva super(s) encodes two forms of the Tva receptor; these proteins are translated from alternatively spliced mRNAs. The normal cellular function of the Tva receptor is unknown; however, the extracellular domain contains a 40-amino-acid, cysteine-rich region that is homologous to the ligand binding region of the low-density lipoprotein receptor (LDLR) proteins. The chicken tva super(s) cDNAs had not yet been fully characterized; we cloned the chicken tva cDNAs from two lines of subgroup A-susceptible chickens, line H6 and line 0. Two types of chicken tva super(s) cDNAs were obtained. These cDNAs encode a longer and shorter form of the Tva receptor homologous to the Tva forms in quail. Two different defects were identified in cDNAs cloned from two different ASLV(A)-resistant inbred chickens, line C and line 7 sub(2). Line C tva super(r) contains a single base pair substitution, resulting in a cysteine-to-tryptophan change in the LDLR-like region of Tva. This mutation drastically reduces the binding affinity of Tva super(R) for the ASLV(A) envelope glycoproteins. Line 7 sub(2) tva super(r2) contains a 4-bp insertion in exon 1 that causes a change in the reading frame, which blocks expression of the Tva receptor.