Interferon-alpha Subtype 11 Activates NK Cells and Enables Control of Retroviral Infection

The innate immune response mediated by cells such as natural killer (NK) cells is critical for the rapid containment of virus replication and spread during acute infection. Here, we show that subtype 11 of the type I interferon (IFN) family greatly potentiates the antiviral activity of NK cells during retroviral infection. Treatment of mice with IFN-alpha 11 during Friend retrovirus infection (FV) significantly reduced viral loads and resulted in long-term protection from virus-induced leukemia. The effect of IFN-alpha 11 on NK cells was direct and signaled through the type I IFN receptor. Furthermore, IFN-alpha 11-mediated activation of NK cells enabled cytolytic killing of FV-infected target cells via the exocytosis pathway. Depletion and adoptive transfer experiments illustrated that NK cells played a major role in successful IFN-alpha 11 therapy. Additional experiments with Mouse Cytomegalovirus infections demonstrated that the therapeutic effect of IFN-alpha 11 is not restricted to retroviruses. The type I IFN subtypes 2 and 5, which bind the same receptor as IFN-alpha 11, did not elicit similar antiviral effects. These results demonstrate a unique and subtype-specific activation of NK cells by IFN-alpha 11.