The host range and interference properties of two closely related feline leukemia variants suggest that they use distinct receptors.

The proviral clones 61E and 61C represent two closely related variants of feline leukemia virus (FeLV) that exhibit significant differences in their biological and pathogenic properties. The major pathogenic determinant has been mapped to the extracellular envelope glycoprotein (Env-SU), but the mechanism by which envelope differences influence pathogenesis is not well understood. Moreover, it is unclear whether these viruses infect the same target cells and/or enter cells using the same receptor. In the present study, we exploited a recently developed single cycle infection assay to examine the host range and interference properties of 61E and 61C FeLVs and found that these two FeLV variants differ significantly in their host ranges and receptor usages. FeLV-61C was found to be an ecotropic virus; the entry of viruses bearing a 61C envelope protein (Env-SU) into cell lines was limited to feline T-cells and feline fibroblasts. In contrast, the host range of 61E includes, in addition to all feline cells examined, some canine, murine, and human cell lines. Feline fibroblast and feline T-cells that expressed 61E envelope were resistant to infection with a virus bearing a 61E Env-SU, whereas these same cells were susceptible to infection by an otherwise similar virus pseudotyped with the 61C Env-SU. This pattern of interference was observed in cells expressing 61E envelope alone, in the absence of other FeLV gene products, demonstrating that interference was mediated specifically by Env-SU. Fibroblast cells chronically infected with a 61C virus were partially resistant to infection with a virus having a 61C Env-SU, but were not resistant to infection by a virus having a 61E Env-SU. On the basis of the current understanding of virus-receptor interactions, the lack of interference between 61E and 61C under conditions where there is significant homologous interference, combined with the differences in their host cell range, leads us to conclude that 61E and 61C use two distinct primary cellular receptors for entry.