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

Nature Structural & Molecular Biology volume 12, pages 60–66 (2005)Cite this article

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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Figure 1: The binding site for FIV SU is localized in the first domain of CD134.
Figure 2: CD134 Asp60 and Asp62 are critical for interaction with FIV.
Figure 3: CD134 Asp60 and Asp62 are exposed at the upper edge of CD134.
Figure 4: Construction of a binding site for FIV in human CD134.
Figure 5: Modeling of feline and human CD134.
Figure 6: CD134L binding to CD134 is species-specific and does not block CD134-FIV interaction.
Figure 7: CXCR4-dependent FIV infection of CD134− cells is facilitated by soluble CD134.

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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, 92037, California, USA

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

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Correspondence to John H Elder.

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Supplementary information

Supplementary Fig. 1

Alignment of feline and human CD134. (PDF 213 kb)

Supplementary Fig. 2

Binding of FIV SU and ACT35 mAb to feline and human CD134 mutants. (PDF 315 kb)

Supplementary Fig. 3

Competitive binding assay between CD134L and FIV SU-Fc for CD134. (PDF 219 kb)

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de Parseval, A., Chatterji, U., Morris, G. et al. Structural mapping of CD134 residues critical for interaction with feline immunodeficiency virus. Nat Struct Mol Biol 12, 60–66 (2005). https://doi.org/10.1038/nsmb872

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