
<ArticleTitle>Identification of envelope determinants of feline leukemia virus subgroup B that permit infection and gene transfer to cells expressing human <prot>Pit1</prot> or <prot>Pit2</prot>.</ArticleTitle>
<AbstractText>The retroviral vector systems that are in common use for gene therapy are designed to infect cells expressing either of two widely expressed phosphate transporter proteins, <prot>Pit1</prot> or <prot>Pit2</prot>. Subgroup B feline leukemia viruses (FeLV-Bs) use the gibbon ape leukemia virus receptor, <prot>Pit1</prot>, as a receptor for entry. Our previous studies showed that some chimeric envelope proteins encoding portions of FeLV-B could also enter cells by using a related receptor protein, <prot>Pit2</prot>, which serves as the amphotropic murine leukemia virus receptor (S. Boomer, M. Eiden, C. C. Burns, and J. Overbaugh, J. Virol. 71:8116--8123, 1997). Here we show that an arginine at position 73 within variable region A (VRA) of the <prot>FeLV-B envelope surface unit</prot> (<prot>SU</prot>) is necessary for viral entry into cells via the human <prot>Pit2</prot> receptor. However, C-terminal <prot>SU</prot> sequences have a dominant effect in determining human <prot>Pit2</prot> entry, even though this portion of the protein is outside known receptor binding domains. This suggests that a combination of specific VRA sequences and C-terminal sequences may influence interactions between <prot>FeLV-B SU</prot> and the human <prot>Pit2</prot> receptor. Binding studies suggest that the C-terminal sequences may affect a postbinding step in viral entry via the <prot>Pit2</prot> receptor, although in all cases, binding of <prot>FeLV-B SU</prot> to human <prot>Pit2</prot> was weak. In contrast, neither the arginine 73 nor specific C-terminal sequences are required for efficient binding or infection with <prot>Pit1</prot>. Taken together, these data suggest that different residues in <prot>SU</prot> may interact with these two receptors. The specific FeLV-Bs described here, which can enter cells using either human Pit receptor, may be useful as envelope pseudotypes for viruses used in gene therapy.</AbstractText>
