Abstract
NK cells are innate lymphocytes that participate in many immune processes encompassing cancer, bacterial and fungal infection, autoimmunity, and even pregnancy and that specialize in antiviral defense. NK cells express inhibitory and activating receptors and kill their targets when activating signals overpower inhibitory signals. The NK cell inhibitory receptors include a uniquely diverse array of proteins named killer cell immunoglobulin-like receptors (KIRs), the CD94 family, and the leukocyte immunoglobulin-like receptor (LIR) family. The NK cell inhibitory receptors recognize mostly major histocompatibility complex (MHC) class I (MHC-I) proteins. Zika virus has recently emerged as a major threat due to its association with birth defects and its pandemic potential. How Zika virus interacts with the immune system, and especially with NK cells, is unclear. Here we show that Zika virus infection is barely sensed by NK cells, since little or no increase in the expression of activating NK cell ligands was observed following Zika infection. In contrast, we demonstrate that Zika virus infection leads to the upregulation of MHC class I proteins and consequently to the inhibition of NK cell killing. Mechanistically, we show that MHC class I proteins are upregulated via the RIGI-IRF3 pathway and that this upregulation is mediated via beta interferon (IFN-β). Potentially, countering MHC class I upregulation during Zika virus infection could be used as a prophylactic treatment against Zika virus.
Original language | American English |
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Article number | e00785-17 |
Journal | Journal of Virology |
Volume | 91 |
Issue number | 22 |
DOIs | |
State | Published - 1 Nov 2017 |
Bibliographical note
Funding Information:This work was supported by the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) (ERC grant agreement 320473-BacNK). Further support came from the Israel Science Foundation, the GIF, the ICRF professorship grant, the Helmholtz Foundation, and the Rosetrees Trust (all to O.M.). O.M. is a Crown Professor of Molecular Immunology. The work was also supported by grants from the Israel Science Foundation and the European Union Seventh Framework Programme (562 FP7/2012-2016) (grant agreement 316655) to D.G.W.
Publisher Copyright:
© 2017 American Society for Microbiology.
Keywords
- MHC class I
- NK cells
- NK escape mechanisms
- Zika virus