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Journal of Virology, August 2001, p. 6841-6849, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.6841-6849.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification of Envelope Determinants of Feline Leukemia Virus Subgroup B That Permit Infection and Gene Transfer to Cells Expressing Human Pit1 or Pit2

James Sugai,1 Maribeth Eiden,2 Maria M. Anderson,1 Neal Van Hoeven,1,3 Christopher D. Meiering,1,4 and Julie Overbaugh1,*

Division of Human Biology, Fred Hutchinson Cancer Research Center,1 and Program in Molecular and Cellular Biology3 and Department of Microbiology,4 University of Washington, Seattle, Washington, and Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, Maryland2

Received 11 December 2000/Accepted 4 May 2001

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, Pit1 or Pit2. Subgroup B feline leukemia viruses (FeLV-Bs) use the gibbon ape leukemia virus receptor, Pit1, 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, Pit2, 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 FeLV-B envelope surface unit (SU) is necessary for viral entry into cells via the human Pit2 receptor. However, C-terminal SU sequences have a dominant effect in determining human Pit2 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 FeLV-B SU and the human Pit2 receptor. Binding studies suggest that the C-terminal sequences may affect a postbinding step in viral entry via the Pit2 receptor, although in all cases, binding of FeLV-B SU to human Pit2 was weak. In contrast, neither the arginine 73 nor specific C-terminal sequences are required for efficient binding or infection with Pit1. Taken together, these data suggest that different residues in SU 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.


* Corresponding author. Mailing address: Division of Human Biology, Fred Hutchinson Cancer Center, 1100 Fairview Ave. N., C3-168, Seattle, WA 98109-1024. Phone: (206) 667-3524. Fax: (206) 667-1535. E-mail: joverbau{at}fhcrc.org.


Journal of Virology, August 2001, p. 6841-6849, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.6841-6849.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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Copyright © 2001 by the American Society for Microbiology. All rights reserved.