THE FELINE LEUKEMIA-VIRUS LONG TERMINAL REPEAT CONTAINS A POTENT GENETIC DETERMINANT OF T-CELL LYMPHOMAGENICITY

Feline leukemia virus (FeLV) is an important pathogen of domestic cats . The most common type of malignancy associated with FeLV is T-cell ly mphoma. SL3-3 (SL3) is a potent T-cell lymphomagenic murine leukemia v irus. Transcriptional enhancer sequences within the long terminal repe ats (LTRs) of SL3 and other murine retroviruses are crucial genetic de terminants of the pathogenicities of these viruses. The LTR enhancer s equences of FeLV contain identical binding sites for some of the trans cription factors that are known to affect the lymphomagenicity of SL3. To test whether the FeLV LTR contains a genetic determinant of lympho magenicity, a recombinant virus that contained the U3 region of a natu rally occurring FeLV isolate, LC-FeLV, linked to the remainder of the genome of SL3 was generated. When inoculated into mice, the recombinan t virus induced T-cell lymphomas nearly as quickly as SL3. Moreover, t he U3 sequences of LC-FeLV were found to have about half as much trans criptional activity in T lymphocytes as the corresponding sequences of SL3. This level of activity was severalfold higher than that of the L TR of weakly leukemogenic Akv virus. Thus, the FeLV LTR contains a pot ent genetic determinant of T-cell lymphomagenicity. Presumably, it is adapted to be recognized by transcription factors present in T cells o f cats, and this yields a relatively high level of transcription that allows the enhancer to drive the requisite steps in the process of lym phomagenesis.