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Structural mapping of CD134 residues critical for interaction with feline immunodeficiency virus

Nature Structural & Molecular Biology volume 12, pages 6066 (2005) | Download Citation

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Abstract

CD134 is a primary binding receptor for feline immunodeficiency virus (FIV), and with CXCR4 facilitates infection of CD4+ T cells. Human CD134 fails to support FIV infection. To delineate the regions important for defining virus specificity of CD134, we exchanged domains between human and feline CD134. The binding site for FIV surface glycoprotein (SU) is located in domain 1, in a region distinct from the natural ligand (CD134L)-binding site. Mutagenesis showed that Asp60 and Asp62 are required for interaction with FIV, and modeling studies localized these two residues to the outer edge of domain 1. Substitutions S60D and N62D, in conjunction with H45S, R59G and V64K, imparted both FIV SU binding and receptor function to human CD134. Finally, we demonstrated that soluble CD134 facilitates infection of CD134 CXCR4+ target cells in a manner analogous to CD4 augmentation of HIV infection.

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Acknowledgements

We wish to thank Y.-C. Lin and S. de Rozières for careful reading of the manuscript and valuable suggestions and J. Wold for manuscript preparation. This research was supported by grant R01AI25825 from the Allergy and Infectious Diseases Institute of the National Institutes of Health.

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  1. Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

    • Aymeric de Parseval
    • , Udayan Chatterji
    • , Garrett Morris
    • , Peiqing Sun
    • , Arthur J Olson
    •  & John H Elder

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The authors declare no competing financial interests.

Corresponding author

Correspondence to John H Elder.

Supplementary information

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  1. 1.

    Supplementary Fig. 1

    Alignment of feline and human CD134.

  2. 2.

    Supplementary Fig. 2

    Binding of FIV SU and ACT35 mAb to feline and human CD134 mutants.

  3. 3.

    Supplementary Fig. 3

    Competitive binding assay between CD134L and FIV SU-Fc for CD134.

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DOI

https://doi.org/10.1038/nsmb872

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