Poster Presentation 8th Australasian Virology Society Meeting and 11th Annual Meeting of the Australian Centre for Hepatitis & HIV Virology Meeting 2015

The Taming of the NK Cell: Manipulation of Human Natural Killer Cell Function and Phenotype by Varicella Zoster Virus Infection (#116)

Tessa M Campbell 1 , Brian P McSharry 1 , Megan Steain 1 , Thomas M Ashhurst 2 , Barry Slobedman 1 , Allison Abendroth 1
  1. Discipline of Infectious Diseases and Immunology, The University of Sydney, Sydney, NSW, Australia
  2. Sydney Cytometry Facility and Discipline of Pathology, The University of Sydney, Sydney, NSW, Australia

Clinical evidence supports a crucial role for natural killer (NK) cells in the control of varicella zoster virus (VZV), the alphaherpesvirus responsible for varicella and herpes zoster. It is accepted that extensive manipulation of the immune response occurs in order for productive infection to be established; however, despite their potent anti-viral capacity, research into how VZV interacts with NK cells remains surprisingly limited. VZV is an established lymphotropic virus, however our findings are the first to demonstrate VZV infection of human peripheral blood NK cells, with remarkably 40% of cells antigen positive after 48 hours. The full cascade of gene expression was confirmed by flow cytometry and immunofluorescence, and cell-sorted infected NK cells were demonstrated to efficiently transmit infection to epithelial cells via cell-associated infection. These findings confirm novel productive infection of human NK cells; while additionally it was found that a marked increase in VZV antigen positive NK cells occurs in the presence of interleukin 2, a proinflammatory cytokine typically elevated during infection. Analysis of NK cell function by cytotoxicity assay further revealed a potent abrogation of cytolytic function with VZV infection. By multi-parameter flow cytometry, human NK cells were subsequently assessed for changes in phenotype following VZV infection, through examining expression of 22 receptors. CD56bright NK cells were found to have lower VZV antigen expression, while a correlation between increasing viral antigen expression and upregulation of the skin-homing marker, CCR8, was revealed. It is intriguing that this chemokine receptor is upregulated on NK cells by VZV infection given the haematological dissemination of virus to the skin during varicella. Notably, the Fc receptor CD16, which regulates antibody-dependent cell-mediated cytotoxicity, was potently downregulated with VZV infection. Additionally, VZV-cultured NK cells showed elevated activation, as detected by CD69 expression. Our findings identify a cell type previously unrecognised as permissive to VZV infection and initiates exploration of the effect of VZV on NK cell function and phenotype.