Soluble forms of the subgroup A avian leukosis virus [ALV(A)] receptor Tvasignificantly inhibit ALV(A) infection in vitro and in vivo

The interactions between the subgroup A avian leukosis virus [ALV(A)] envel ope glycoproteins and soluble forms of the ALV(A) receptor Tva were analyze d both in vitro and in vivo by quantitating the ability of the soluble Tva proteins to inhibit ALV(A) entry into susceptible cells. Two soluble Tva pr oteins were tested: the 83-amino-acid Tva extracellular region fused to two epitope tags (sTva) or fused to the constant region of the mouse immunoglo bulin G heavy chain (sTva-mIgG). Replication-competent ALV-based retroviral vectors,,with subgroup B or C env were used to deliver and express the two soluble tv-a (sba) genes in avian cells. In vitro, chicken embryo fibrobla sts or DF-1 cells expressing sTva or sTva-mIgG proteins were much more resi stant to infection by ALV(A) (similar to 200-fold) than were control cells infected by only the vector. The antiviral effect was specific for ALV(A), which is consistent with a receptor interference mechanism. The antiviral e ffect of sTva-mIgG was positively correlated with the amount of sTva-mIgG p rotein. In vivo, the stva genes were delivered and expressed in line 0 chic ken embryos by the ALV(B)-based vector RCASBP(B). Viremic chickens expresse d relatively high levels of stva and stva-mIgG RNA in a broad range of tiss ues. High levels of sTva-mIgG protein were detected in the sera of chickens infected with RCASBP(B)stva-mIgG. Viremic chickens infected with RCASBP(B) alone, RCASBP(B)stva, or RCASBP(B)stva-mIgG were challenged separately wit h ALV(A) and ALV(C). Both sTva and sTva-mIgG significantly inhibited infect ion by ALV(A) (95 and 100% respectively) but had no measurable effect on AL V(C) infection. The results of this study indicate that a soluble receptor can effectively block infection of at least some retroviruses and demonstra tes the utility of the ALV experimental system in characterizing the mechan ism(s) of viral entry.