The functional impairment of natural killer cells during influenza virus infection

Natural killer (NK) cells have a critical role in clearing influenza virus, which primarily infects the lung epithelial cells. However, the ability of influenza virus to infect and manipulate NK cells has not been studied. In this context, we hypothesized that influenza virus can target NK cells leading to a functional impairment in their ability to mediate cytotoxicity and cytokine/chemokine generations. Here, we show influenza virus, PR8, can enter and infect NK cells. This infection did not alter the expression levels of activating, inhibitory or developmental receptors of NK cells. However, infection of NK cells by PR8 reduced the cytotoxicity to tumor cells that represent 'induced-self' and 'missing-self'. PR8-infection also significantly downregulated the NCR1, NKG2D, Nkpr1c, Ly49D and CD244 receptors-mediated generation of pro-inflammatory cytokines and chemokines. Mutations in the non-structural protein 1 (NS1) of influenza virus further augmented the functional impairment of NK cells. Our observations show the presence of a new, but yet to be explored, mechanism by which the influenza virus can evade immune detection.