Cellular transporter proteins have been identified as the receptors for retroviruses. The receptor for the amphotropic murine retroviruses and Gibbon ape leukemia virus are related phosphate transporters (RAM-1 and GLVR-1, respectively). The receptor for the ecotropic murine retrovirus is a basic amino acid transporter (CAT-1). The overall goal of these studies are to analyze the structure and dual functions of these receptors/transporters in order to understand their role in viral pathogenesis as well as to improve their use for gene delivery.
Five specific aims are proposed: 1) Understand the structures, post-translational modifications, cellular distributions, and mechanisms of function of the RAM-1 and GLVR-1 proteins. Of particular interest is the role of phosphorylation in enhancing the activities of the RAM-1 protein in both transport and infection. 2) Identify factors that functionally and/or physically interact with RAM-1 and study the functions of these interactions. 3) Pursue host cell factor(s) that could collaborate with receptors in a pathway that leads to fusion of the cell and viral membranes. A model is presented that the assembly of multivalent virus-receptor clusters may be necessary for completion of this pathway 4) Determine whether the antiviral drug, phosphate analog, forscarnet (phosphonoformate) inhibits the RAM-1 and GLVR-1 transporter activities. 5) Analyze the role of glycosylation in blocking infection of hamster cells by ecotropic and amphotropic mouse retroviruses.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA025810-22
Application #
6172425
Study Section
Virology Study Section (VR)
Program Officer
Cole, John S
Project Start
1997-07-01
Project End
2002-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
22
Fiscal Year
2000
Total Cost
$203,784
Indirect Cost
Name
Oregon Health and Science University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Tailor, C S; Lavillette, D; Marin, M et al. (2003) Cell surface receptors for gammaretroviruses. Curr Top Microbiol Immunol 281:29-106
Marin, Mariana; Lavillette, Dimitri; Kelly, Sean M et al. (2003) N-linked glycosylation and sequence changes in a critical negative control region of the ASCT1 and ASCT2 neutral amino acid transporters determine their retroviral receptor functions. J Virol 77:2936-45
Lavillette, Dimitri; Marin, Mariana; Ruggieri, Alessia et al. (2002) The envelope glycoprotein of human endogenous retrovirus type W uses a divergent family of amino acid transporters/cell surface receptors. J Virol 76:6442-52
Tailor, C S; Marin, M; Nouri, A et al. (2001) Truncated forms of the dual function human ASCT2 neutral amino acid transporter/retroviral receptor are translationally initiated at multiple alternative CUG and GUG codons. J Biol Chem 276:27221-30
Tailor, C S; Nouri, A; Kabat, D (2000) Cellular and species resistance to murine amphotropic, gibbon ape, and feline subgroup C leukemia viruses is strongly influenced by receptor expression levels and by receptor masking mechanisms. J Virol 74:9797-801
Marin, M; Tailor, C S; Nouri, A et al. (2000) Sodium-dependent neutral amino acid transporter type 1 is an auxiliary receptor for baboon endogenous retrovirus. J Virol 74:8085-93
Tailor, C S; Nouri, A; Kabat, D (2000) A comprehensive approach to mapping the interacting surfaces of murine amphotropic and feline subgroup B leukemia viruses with their cell surface receptors. J Virol 74:237-44
Tailor, C S; Nouri, A; Zhao, Y et al. (1999) A sodium-dependent neutral-amino-acid transporter mediates infections of feline and baboon endogenous retroviruses and simian type D retroviruses. J Virol 73:4470-4
Tailor, C S; Willett, B J; Kabat, D (1999) A putative cell surface receptor for anemia-inducing feline leukemia virus subgroup C is a member of a transporter superfamily. J Virol 73:6500-5
Marin, M; Tailor, C S; Nouri, A et al. (1999) Polymorphisms of the cell surface receptor control mouse susceptibilities to xenotropic and polytropic leukemia viruses. J Virol 73:9362-8

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