Blockade of Interferon Beta, but Not Interferon Alpha, Signaling Controls Persistent Viral Infection

SUMMARY Although type I interferon (IFN-I) is thought to be beneficial against microbial infections, persistent viral infections are characterized by high interferon signatures suggesting that IFN-I signaling may promote disease pathogenesis. During persistent lymphocytic choriomeningitis virus (LCMV) infection, IFNa and IFNb are highly induced early after infection, and blocking IFN-I receptor (IFNAR) signaling promotes virus clearance. We assessed the specific roles of IFNb versus IFNa in controlling LCMV infection. While blockade of IFNb alone does not alter early viral dissemination, it is important in determining lymphoid structure, lymphocyte migration, and anti-viral T cell responses that lead to accelerated virus clearance, approximating what occurs during attenuation of IFNAR signaling. Comparatively, blockade of IFNa was not associated with improved viral control, but with early dissemination of virus. Thus, despite their use of the same receptor, IFNb and IFNa have unique and distinguishable biologic functions, with IFNb being mainly responsible for promoting viral persistence.