Amino acid residues Tyr-67, Asn-72, and Asp-73 of the TVB receptor are important for subgroup E avian sarcoma and leukosis virus interaction.

The chicken TVB(S1) protein serves as the cellular receptor for the cytopathic subgroups B and D avian sarcoma and leukosis viruses (ASLVs) as well as for the non-cytopathic subgroup E ASLV. Previous studies had mapped the subgroup B viral interaction determinants to a region that was located between residues 32 and 46 of TVB(S1) [J. Virol. 76 (2002) 5404]. To gain a greater insight into ASLV Env-receptor interactions and the possible role of these interactions in viral cytopathic effects, we employed a homolog-scanning mutagenesis approach to identify amino acid residues important for subgroup E viral receptor function by exchanging amino acid residues between TVB(S1) and its human homolog, DR5. These studies identified residues Tyr-67, Asn-72, and Asp-73 of TVB(S1) as important subgroup E viral interaction determinants. Intriguingly, these three residues are conserved between TVB(S1) and DR5, demonstrating that the human protein contains critical subgroup E viral interaction determinants, but in this context, they cannot support viral entry. These data confirm that the molecular determinants of the TVB receptor required for subgroup E viral entry are completely distinct from those used by subgroup B viruses.