Role of Natural Killer and Gamma-Delta T cells in West Nile Virus Infection

Wang, Tian; Welte, Thomas

Activated NK cells inhibited WNV infection of Vero cells through both antibody-dependent cellular cytotoxicity (ADCC) and non-cytolytic activities, such as secretion of interferon (IFN)-ï§ï€ [29] . Both host factors and microbial signals are involved in triggering NK cell activation during viral infection. NK cells can detect microbial signals by stimulation of their pathogen recognition receptors (PRRs), such as toll-like receptor (TLR) or RIG-I like receptor (RLR), or being activated by innate cytokines predominantly produced by infected DCs [43, 44] . By using the integrated system biology approach, Suthar et al. [36] have recently demonstrated that the liver-specific NK cell activation during WNV infection is regulated by two innate immune signaling pathways, including RLR and IFN. In WNV-infected liver, IFN functions intrinsically in regulation of NK cell activation, proliferation, and maturation; whereas RLR-mediated type 1 IFN production in DCs imparts signaling extrinsically via crosstalk to NK cells and triggers their activation. NK cells are also known to sense microbial and non-microbial signals from target cells through a variety of activating and inhibitory receptors, which influence cytotoxicity towards virus-infected cells and cancerous cells [45] . Upon WNV infection, interaction of the activating receptor NKp44 of human NK cells with domain III of the WNV envelope (E) protein was shown to be an important step in triggering both IFN- secretion and cytolytic activity of NK cells during infection [46] .