The role of endogenous FeLV in the infectivity and genomic stability of FeLV subgroup A

Feline leukemia viruses (FeLV) are simple retroviruses associated with certain cancers and are used as an important model for studying carcinogenic mechanisms of retroviruses. Of the three FeLV subgroups A, B and C, FeLV-B is generated from recombination between FeLV-A and endogenous FeLV (enFeLV). In a previous study of two closely related FeLV-A molecular clones, pF6A and pFRA, FRA was found to be more pathogenic and recombinogenic. In the current studies, FRA and F6A were shown to be equally infectious to feline lymphoid (3201) and fibroblast (FEA) cells. However, FRA was significantly more recombinogenic than F6A in 3201 cells but not in FEA cells. The probable mechanism for the increased recombinogenicity of FRA in the 3201 cells was traced to the higher amount of enFeLV RNA present in the FRA virion. This increase was shown not to be due to a selective increase in enFeLV expression by FRA infected cells. These results indicate that FRA copackages more enFeLV RNA than F6A. To study the role of the variation in pol region between F6A and FRA, the pol regions were switched between pF6A and pFRA. Although the transfection of 3201 cells with the generated chimeras resulted in infectious viruses, no recombinants were detected indicating the presence of other factors that might interact with pol to promote recombination.; In a previous study, the inoculation of FRA-GFP in feline fibroblast cells resulted in stable GFP expression. In our hands, the pFRA-GFP inoculation in vivo and in 3201 cells in vitro resulted in unstable FRA-GFP virus.; Because F6A and FRA recombinogenicity and FRA-GFP stability were cell-dependent, we investigated enFeLV RNA expression in feline lymphoid and fibroblast cells and tissues. Lymphoid tissues were found to express high level of enFeLV RNA while the ileum, salivary gland and brain tissues were under the detection limit as determined by RT-PCR. The 3201 cells were found to have 181 times more enFeLV RNA than fibroblast cells. In conclusion, these studies demonstrated that the cell-dependency relies on the expression of enFeLV RNA.