Zika virus escapes NK cell detection by upregulating MHC class I molecules.

5 years ago

Zika virus escapes NK cell detection by upregulating MHC class I molecules.

Mandelboim O, Weisblum Y, Oiknine-Djian E, Glasner A, Wolf DG, Diab M, Panet A

NK cells are innate lymphocytes that participate in many immune processes encompassing cancer, bacterial and fungal infection, autoimmunity and even pregnancy and are specialize in anti-viral defense. NK cells express inhibitory and activating receptors and kill their targets when activating signals overpower the inhibitory ones. The NK cell inhibitory receptors compose of a uniquely diverse array of proteins named Killer-cell immunoglobulin-like receptors (KIRs) the CD94 family and the leukocyte immunoglobulin like receptor family (LIR). The NK inhibitory receptors recognize mostly MHC class 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, especially with NK cells is unclear. Here we show that Zika virus infection is barely sensed by NK cells, as little or no increase in the expression of activating NK cell ligands was observed. In contrast, we demonstrate that Zika virus infection leads to the upregulation of MHC class I proteins and consequently to inhibition of NK cell killing. Mechanistically, we show that the upregulation of MHC class I occurs via the RIGI-IRF3 pathway, and is mediated via IFNβ. Potentially, countering MHC class I upregulation during Zika virus infection could be used as a prophylactic treatment against Zika virus.IMPORTANCE NK cells are innate lymphocytes, which recognize and eliminate various pathogens, and are mostly known for their role in controlling viral infections. NK cells express inhibitory and activating receptors and kill or spare their targets based on integration of inhibitory and activating signals. Zika virus has recently emerged as a major threat to humans due to its pandemic potential and association with birth defects. The role of NK cells in Zika virus infection is largely unknown. Here, we demonstrate that Zika virus infection is almost undetected by NK cells, as expression of activating ligands for NK cells are not induced following Zika infection. We identified a mechanism whereby Zika virus sensing via the RIGI IRF3 pathway resulted in an IFNβ mediated upregulation of MHC-I molecules, and inhibition of NK cell activity. Countering MHC class I upregulation and boosting NK cell activity may be employed as a prophylactic measure to combat Zika virus infection.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28878071

DOI: PubMed:28878071