Profiling the natural killer cell response to acute Zika virus infection by mass cytometry 4258

Abstract Description Zika virus (ZIKV) is a mosquito-borne flavivirus of global concern due to its ability to cause congenital neurological defects. Natural killer cells are innate lymphocytes which can directly kill virus-infected cells. It is thought that NK cells are protective against ZIKV, although the mechanisms by which NK cells detect and respond to ZIKV are not well understood. Here, we evaluated NK cell receptor expression on isolated NK cells and corresponding NK receptor ligand expression on PBMCs from a Panamanian cohort of ZIKV-infected participants and healthy control participants using mass cytometry. We found that during acute ZIKV infection NK cells express high levels of activation markers, proliferative markers, and cytotoxic effector proteins, indicating that NK cells are mounting a response to ZIKV. Interestingly, not all markers elevated during acute infection returned to baseline upon recovery, suggesting ZIKV infection may have potential long-term effects on NK cell function. Analysis of NK receptor ligand expression on ZIKV-infected cells in vitro revealed virus-induced modulation of NK ligands in a manner suggestive of viral evasion of NK killing. Current work is focused on identifying specific receptors that mediate NK cell activation and on understanding how ZIKV infection alters NK cell functions in vitro and in patients. This work will improve our understanding of the NK cell response to ZIKV infection which will aid in the development of vaccines and therapeutics. Funding Sources Supported by the Chan-Zuckerberg Biohub (to C.A.B.) and the Stanford Medicine Pandemic Preparedness Hub (to T.R.B.) Topic Categories Viral Immunology (VIR)