A novel truncated env gene isolated from a feline leukemia virus-induced thymic lymphosarcoma

We PCR amplified the exogenous feline leukemia virus (FeLV)-related env gen e species from lymphosarcomas induced by intradermally administered plasmid DNA of either the prototype FeLV, subgroup A molecular clone, F6A, or a ne w molecular clone, FeLV-A, Rickard strain (FRA). Of the nine tumors examine d, six showed the presence of deleted env species of variable sizes in the tumor DNA, One env mutant, which was detected in a FRA-induced thymic lymph osarcoma, had a large internal deletion beginning from almost the N-termina l surface glycoprotein (SU) up to the middle region of the transmembrane (T M) protein of the env gene. The deduced polypeptide of this truncated env ( tenv) retained the complete signal peptide and seven amino acids of the N-t erminal mature SU of FRA env gene, followed by eight amino acids from the f rameshift in the TR I region. To study the biological function of tenv, we used a murine retrovirus vector to produce amphotropic virions, Infection o f feline fibroblasts (H927), human fibrosarcoma cells (HT1080), or human B- lymphoma cells (Raji) led to pronounced cytotoxicity, while the tenv virus did not induce significant cytotoxicity to feline T-lymphoma cells (3201B) or human T-lymphoma cells (CEM). Together, these results convincingly demon strated that the genetic events that led to truncation in the env gene occu rred de novo in FeLV lymphomagenesis and that such a product, tenv could in duce cytotoxicity to fibroblastic and B-lymphoid cells but not to T-lymphoi d tumor cells. This type of selective toxicity might be potentially importa nt in the development of the neoplastic disease.