Zika virus escapes NK cell detection by upregulating major histocompatibility complex class I molecules

Ariella Glasner, Esther Oiknine-Djian, Yiska Weisblum, Mohammad Diab, Amos Panet, Dana G. Wolf, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


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 languageAmerican English
Article numbere00785-17
JournalJournal of Virology
Issue number22
StatePublished - 1 Nov 2017

Bibliographical note

Publisher Copyright:
© 2017 American Society for Microbiology.


  • MHC class I
  • NK cells
  • NK escape mechanisms
  • Zika virus


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