Residues Y142, I143, T146, Q206, S215, R228, G267, and M268 in the surface glycoprotein of FGV-like subgroup A avian leukosis virus are the key sites determining Tva receptor binding and infectivity.

Abstract

Avian leukosis virus subgroup A (ALV-A) invades cells through the specific recognition of the cellular receptor Tva by its encoded surface glycoprotein gp85. Certain Fowl glioma-inducing virus (FGV) strains and their variants belong to ALV-A, but their gp85 proteins differ substantially from classical ALV-A strains. To identify the key residues in the gp85 of FGV-like ALV-A strain 2023ZW001 that determine Tva-binding affinity and infectivity, a strategy of substituting the corresponding gp85 residues between ALV-A 2023ZW001 and ALV-E ev-1 (which uses Tvb as its receptor) was adopted. A series of chimeric gp85 proteins for receptor binding assays were expressed, and multiple recombinant retroviral vectors RCASBP(ZW/ev-1)-EGFP/mCherry were constructed to transfect DF-1 cells for replication capacity analysis. The results showed that host range region 1 (hr1), host range region 2 (hr2), and variable region 3 (vr3) play a decisive role in mediating viral infection. Among these regions, residues 140-146 in hr1 and residues 267-273 in vr3 are the indispensable regions for 2023ZW001 to bind the receptor and mediate viral infection. Residues Y142, I143, and T146 in hr1; residues Q206, S215, and R228 in hr2; and as residues G267 and M268 in vr3 are the key sites determining Tva receptor binding and infectivity. This study indicated that hr1 and hr2 of the FGV-like ALV-A strain contain the major receptor interaction determinants, while vr3 also plays a key role in receptor-binding affinity and infectivity.