Insertion/deletion mutations within tva receptor gene confer chicken resistance to infection by avian leukosis virus subgroups A and K

The classic subgroup A (ALV-A) and newly emerging subgroup K (ALV-K) of avian leukosis virus are two major pathogens responsible for avian leukemia in chickens, posing substantial threats to global poultry industry. Both viruses share a Tva protein encoded by the tva gene as a receptor to gain the entry into the host cells. In this study, we described the identifications of two alleles of the tva receptor gene in Qingyuan partridge chicken, which possesses an 11-nucleotide (GCTGCCCACCC) insertion and a 6-nucleotide (ACCTCC) deletion independently located in exon 1 of the tva receptor gene. The natural 11-nucleotide insertion causes a frameshift in the reading frame of the tva cDNA, which presumably blocks the expression of the normal tva allele and results resistance in chicken against infection by ALV-A and ALV-K. The natural 6-nucleotide deletion leads to a Tva receptor protein missing the amino acids residues T21 and S22, which appeared dysfunctional to mediate the viral entry. As a result, we observed that the deletion mutation in the tva receptor gene significantly reduced the susceptibility to infection by ALV-A and ALV-K in vitro and in vivo, and significantly reduced the binding capacity of the Tva receptor protein to the envelope glycoproteins of ALV-A and ALV-K in our subsequent analysis. Taken together, these findings not only provide evidence that the insertion and deletion mutations within the tva receptor gene confer chicken resistance to infection by ALV-A and ALV-K but also provide ideal targets for selective breeding of ALV-A and ALV-K resistance in chicken.