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

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, IFN alpha and IFN beta are highly induced early after infection, and blocking IFN-I receptor (IFNAR) signaling promotes virus clearance. We assessed the specific roles of IFN beta versus IFN alpha in controlling LCMV infection. While blockade of IFN beta 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 IFN alpha was not associated with improved viral control, but with early dissemination of virus. Thus, despite their use of the same receptor, IFN beta and IFN alpha have unique and distinguishable biologic functions, with IFN beta being mainly responsible for promoting viral persistence.