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Journal of Virology, August 2002, p. 8069-8078, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8069-8078.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Genetic and Biochemical Analyses of Receptor and Cofactor Determinants for T-Cell-Tropic Feline Leukemia Virus Infection

Adam S. Lauring,1,2,{dagger} Heather H. Cheng,1,2 Maribeth V. Eiden,3 and Julie Overbaugh2*

Program in Molecular and Cellular Biology, University of Washington,1 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington,2 Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland3

Received 18 January 2002/ Accepted 9 May 2002

Entry by retroviruses is mediated through interactions between the viral envelope glycoprotein and the host cell receptor(s). We recently identified two host cell proteins, FeLIX and Pit1, that are necessary for infection by cytopathic, T-cell-tropic feline leukemia viruses (FeLV-T). Pit1 is a classic multiple transmembrane protein used as a receptor by several other simple retroviruses, including subgroup B FeLV (FeLV-B), and FeLIX is a secreted cellular protein expressed from endogenous FeLV-related sequences (enFeLV). FeLIX is nearly identical to FeLV-B envelope sequences that encode the N-terminal half of the viral surface unit (SU), because these FeLV-B sequences are acquired by recombination with enFeLV. FeLV-B SUs can functionally substitute for FeLIX in mediating FeLV-T infection. Both of these enFeLV-derived cofactors can efficiently facilitate FeLV-T infection only of cells expressing Pit1, not of cells expressing the related transport protein Pit2. We therefore have used chimeric Pit1/Pit2 receptors to map the determinants for cofactor binding and FeLV-T infection. Three distinct determinants appear to be required for cofactor-dependent infection by FeLV-T. We also found that Pit1 sequences within these same domains were required for binding by FeLIX to the Pit receptor. In contrast, these determinants were not all required for receptor binding by the FeLV-B SU cofactors used in this study. These data indicate that cofactor binding is not sufficient for FeLV-T infection and suggest that there may be a direct interaction between FeLV-T and the Pit1 receptor.


* 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.

{dagger} Present address: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-0119.


Journal of Virology, August 2002, p. 8069-8078, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8069-8078.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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