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Herpes simplex virus evades natural killer T cell recognition by suppressing CD1d recycling

Nature Immunology volume 7, pages 835–842 (2006)Cite this article

Abstract

Natural killer T cells, which are stimulated by lipids presented by CD1d molecules, are crucial in antiviral host defense. How viruses evade natural killer T cell recognition remains unclear. Here we show that infection with herpes simplex virus type 1 (HSV-1) reduced CD1d surface expression on antigen-presenting cells. HSV-1 did not inhibit CD1d protein synthesis or enhance constitutive CD1d endocytosis. Instead, HSV-1 prevented the reappearance of endocytosed CD1d on the cell surface by redistributing endocytosed CD1d to the lysosome limiting membrane. HSV-1 might also inhibit the transport of newly synthesized CD1d to the cell surface. Such inhibition of CD1d surface expression impaired antigen-presenting cell–mediated stimulation of natural killer T cells, supporting the idea that this mechanism may be an important HSV-1 immune evasion strategy.

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Figure 1: HSV-1 downregulates surface CD1d in antigen-presenting cells.
Figure 2: Inhibition of protein synthesis is not responsible for HSV-1-mediated downregulation of surface CD1d expression.
Figure 3: HSV-1-mediated downregulation of surface CD1d expression inhibits NKT cell activation.
Figure 4: Biogenesis and surface arrival of CD1d in HSV-1 infected cells.
Figure 5: Recycling of CD1d to the cell surface is impaired in HSV-1-infected cells.
Figure 6: CD1d is trapped in internal vesicles after HSV-1 infection.

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Acknowledgements

We thank A. Iwasaki, R. Medzhitov, P. Lehner, A. Chow and D.R. Peaper for discussions, and M. Pypaert (Yale Cell Biology Imaging Facility, New Haven, Connecticut) for the immuno-electron microscopic analysis. Supported by the National Institutes of Health (AI059167 to P.C.), Howard Hughes Medical Institute (P.C.) and Cancer Research Institute (W.Y.).

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Author notes

  1. Anindya Dasgupta

    Present address: Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, Beaverton, Oregon, 97006, USA

Authors and Affiliations

  1. Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, 06520-8011, Connecticut, USA

    Weiming Yuan, Anindya Dasgupta & Peter Cresswell

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Contributions

W.Y. and A.D. did the experiments; P.C. supervised the work.

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Correspondence to Peter Cresswell.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

CD1d is relocalized from internal vesicles to the limiting membrane of multivesicular bodies after HSV-1 infection. (PDF 10714 kb)

Supplementary Video 1

Three-dimensional reconstruction of an infected Hela.CD1d.eGFP cell (24 h after infection with vhs-deficient HSV-1). (MPG 1804 kb)

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Yuan, W., Dasgupta, A. & Cresswell, P. Herpes simplex virus evades natural killer T cell recognition by suppressing CD1d recycling. Nat Immunol 7, 835–842 (2006). https://doi.org/10.1038/ni1364

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