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Science 10 March 2000:
Vol. 287. no. 5459, pp. 1828 - 1830
DOI: 10.1126/science.287.5459.1828
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Reports

Identification of a Cellular Cofactor Required for Infection by Feline Leukemia Virus

Maria M. Anderson, 12 Adam S. Lauring, 13 Cara C. Burns, 2* Julie Overbaugh 12dagger

Retroviral infection involves continued genetic variation, leading to phenotypic and immunological selection for more fit virus variants in the host. For retroviruses that cause immunodeficiency, pathogenesis is linked to the emergence of T cell-tropic, cytopathic viruses. Here we show that an immunodeficiency-inducing, T cell-tropic feline leukemia virus (FeLV) has evolved such that it cannot infect cells unless both a classic multiple membrane-spanning receptor molecule (Pit1) and a second coreceptor or entry factor are present. This second receptor component, which we call FeLIX, was identified as an endogenously expressed protein that is similar to a portion of the FeLV envelope protein. This cellular protein can function either as a transmembrane protein or as a soluble component to facilitate infection.

1 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
2 Department of Microbiology,
3 Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195, USA.
*   Present address: Respiratory and Enteric Virus Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

dagger    To whom correspondence should be addressed. E-mail: joverbau{at}fhcrc.org

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Genetic and Biochemical Analyses of Receptor and Cofactor Determinants for T-Cell-Tropic Feline Leukemia Virus Infection.
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A. S. Lauring, M. M. Anderson, and J. Overbaugh (2001)
J. Virol. 75, 8888-8898
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Receptor Binding Transforms the Surface Subunit of the Mammalian C-Type Retrovirus Envelope Protein from an Inhibitor to an Activator of Fusion.
A. L. Barnett and J. M. Cunningham (2001)
J. Virol. 75, 9096-9105
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Receptors and Entry Cofactors for Retroviruses Include Single and Multiple Transmembrane-Spanning Proteins as well as Newly Described Glycophosphatidylinositol-Anchored and Secreted Proteins.
J. Overbaugh, A. D. Miller, and M. V. Eiden (2001)
Microbiol. Mol. Biol. Rev. 65, 371-389
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Selection Forces and Constraints on Retroviral Sequence Variation.
J. Overbaugh and C. R. M. Bangham (2001)
Science 292, 1106-1109
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Functional Characterization of the N Termini of Murine Leukemia Virus Envelope Proteins.
C.-W. Lu and M. J. Roth (2001)
J. Virol. 75, 4357-4366
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Activation of Membrane Fusion by Murine Leukemia Viruses Is Controlled in cis or in trans by Interactions between the Receptor-Binding Domain and a Conserved Disulfide Loop of the Carboxy Terminus of the Surface Glycoprotein.
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