Salvage pathway of vitamin B12 absorption in chickens with mutant tumor virus a receptor

Abstract

The tumor virus A receptor (TVA), a member of the low-density lipoprotein receptor (LDLR) family, serves as an entry receptor for Avian Leukosis Virus (ALV) subgroups A and K, as well as a receptor for vitamin B₁₂ bound to transcobalamin. Naturally occurring genetic variants in the TVA gene determine susceptibility or resistance to ALV-A and -K, but the effects of these mutated TVA on vitamin B₁₂ uptake have not been investigated systemically. We found four TVA variants comprising the wild type (TVA^WT), a single nucleotide polymorphism variant (TVA^SNP), and two partial deletions in the splicing branch point region (TVA^R). This study investigates the relationship between the various genotypes of TVA alleles and uptake of vitamin B₁₂ in chickens. A protein interaction model suggested that mutant TVAs (i.e., TVA^SNP, TVA^R) may have reduced ability to take up vitamin B₁₂ due to a disrupted LDL-A domain, a pivotal region involved in vitamin B₁₂ uptake; however, we found no significant difference in absorption of vitamin B₁₂ in TVA^WT and TVA^SNP chickens, or levels of its metabolite in serum. Notably, TVA^R chickens had significantly higher levels of vitamin B₁₂ than TVA^WT chickens, a finding contrary to the predicted lower uptake. Expression of vitamin B₁₂ carrier related genes (i.e., AMN, GIF, and TCN2) in chickens showed a stepwise increase: TVA^WT > TVA^SNP > TVA^R. These results suggest a mechanism by which mutant TVA chickens with a disrupted TVA protein acquire natural resistance to ALV-A -K, with no impairment of vitamin B₁₂ metabolism.