Feline Pit2 functions as a receptor for subgroup B feline leukemia viruses

Different subgroups of feline leukemia virus (FeLV) use different host cell receptors for entry. Subgroup A FeLV (FeLV-A) is the virus that is transmi tted from cat to cat, suggesting that cells expressing the FeLV-A receptor are important targets at the earliest stages of infection. FeLV-B evolves f rom FeLV-A in the infected cat through acquisition of cellular sequences th at are related to the FeLV envelope gene. FeLV-Bs have been shown to infect cells using the Pit1 receptor, and some variants can infect cells at a low er efficiency using Pit2. Because these observations were made using recept or proteins of human or rodent origin, the role that Pit1 and Pit2 may play in FeLV-B replication in the cat is unclear. In this study, the feline Pit receptors were cloned and tested for their ability to act as receptors for different FeLV-Bs. Some FeLV-Bs infected cells expressing feline Pit2 and feline Pit1 with equal high efficiency. Variable region A (VRA) in the puta tive receptor-binding domain (RBD) was a critical determinant for both feli ne Pit1 and feline Pit2 binding, although other domains in the RBD appear t o influence how efficiently the FeLV-B surface unit can bind to feline Pit2 and promote entry via this receptor. An arginine residue at position 73 in VRA was found to be important for envelope binding to feline Pit2 but not feline Pit1. Interestingly, this arginine is not found in endogenous FeLV s equences or in recombinant viruses recovered from feline cells infected wit h FeLV-A. Thus, while FeLV-Bs that are able to use feline Pit2 can evolve b y recombination with endogenous sequences, a subsequent point mutation duri ng reverse transcription may be needed to generate a virus that can efficie ntly enter the cells using the feline Pit2 as its receptor. These studies s uggest that cells expressing the feline Pit2 protein are likely to be targe ts for FeLV-B infection in the cat.