Long terminal repeat regions from exogenous but not endogenous feline leukemia viruses transactivate cellular gene expression

We have previously reported that the long terminal repeat (LTR) region of f eline leukemia viruses (FeLVs) can enhance expression of certain cellular g enes such as the collagenase IV gene and MCP-1 in trans (S, K, Ghosh and D, V. Faller, J, Virol, 73:4931-4940, 1999), Genomic DNA of all healthy felin e species also contains LTR-like sequences that are related to exogenous Fe LV LTRs. In this study, we evaluated the cellular gene transactivational po tential of these endogenous FeLV LTR sequences. Unlike their exogenous FeLV counterparts, neither nearly full-length endogenous FeLV molecular clones (CFE-6 and CFE-16) nor their isolated LTRs were able to activate collagenas e IV gene or MCP-1 expression in transient transfection assays. We had also demonstrated previously that production of an RNA transcript from exogenou s FeLV LTRs correlates with their transactivational activity. In the presen t study, we demonstrate that the endogenous FeLV LTRs do not generate LTR-s pecific RNA transcripts in the feline embryo fibroblast cell line AH927. Fu rthermore, infection of AH927 cells by an exogenous FeLV subgroup A virus d id not induce production of such LTR-specific transcripts from the endogeno us proviral genomes, although the LTR-specific transcripts from the exogeno us virus were readily detected. Finally, LTR-specific transcripts were not generated in BALB/3T3 cells transiently transfected with isolated CFE-6 LTR in contrast to transfections with LTRs from exogenous viruses. Our data th us suggest that the inability of endogenous FeLV LTRs in gene transactivati on is not due to cell line specificity or presence of any upstream inhibito ry cis-acting element. Endogenous, nonleukemogenic FeLV LTRs, therefore, do not transactivate cellular gene expression, and this property appears to b e specific to exogenous, leukemogenic FeLVs.