Selection of feline leukemia virus envelope proteins from a library by functional association with a murine leukemia virus envelope

Libraries of feline leukemia virus subgroup A (FeLV-A)-derived envelope (Env) proteins with random peptides incorporated into the cell-targeting region were screened for productive gene delivery to the PC-3 human prostate cell line. In order to increase the efficiency of recovering and testing functional clones, the screen was performed in the presence of a replication-competent 4070A Env-expressing virus under conditions of viral interference. The Env proteins resulting from this library screen were able to mediate gene delivery to 4070A-infected human PC-3, DU145 prostate and TE671 rhabdomyosarcoma cells in the presence, but not absence, of 4070A helper virus. FeLV-A, FeLV-B and Moloney murine leukemia virus (Mo-MuLV) Env proteins were unable to substitute for 4070A Env. Flow cytometry and Western blot analyses indicated increased cell-surface expression and virion incorporation of library-derived Env proteins in the presence of 4070A Env. Interference assays on cells infected with both 4070A and FeLV-B are consistent with the combination of library-derived and 4070A Env proteins utilizing the Pit1 receptor.