THE HOST-RANGE AND INTERFERENCE PROPERTIES OF 2 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 de terminant has been mapped to the extracellular envelope glycoprotein ( Env-SU), but the mechanism by which envelope differences influence pat hogenesis is not well understood. Moreover, it is unclear whether thes e viruses infect the same target cells and/or enter cells using the sa me receptor. In the present study, we exploited a recently developed s ingle cycle infection assay to examine the host range and interference properties of 61E and 61C FeLVs and found that these two FeLV variant s 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 incl udes, in addition to all feline cells examined, some canine, murine, a nd human cell lines. Feline fibroblast and feline T-cells that express ed 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, i n the absence of other FeLV gene products, demonstrating that interfer ence 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 o f virus-receptor interactions, the lack of interference between 61E an d 61C under conditions where there is significant homologous interfere nce, combined with the differences in their host cell range, leads us to conclude that 61E and 61C use two distinct primary cellular recepto rs for entry. (C) 1998 Academic Press.