S-7: Lindenmann looked for a herring and found a smallmouth bass. We looked for Dr. Jekyll and found Mr. Hyde: Interferon induces persistent viral infection
Hallmarks of persistent viral infections are T cell exhaustion, expression of negative immune regulator (NIR) IL-10 and PD-L1, elevated interferon (IFN) signatures, a chronic immune activation, and often disorganized secondary lymphoid tissue architecture. Utilizing the established and optimal experimental model of viral persistence, lymphocytic choriomeningitis virus (LCMV) Clone 13 infection of mice, we discovered that blockade of type I IFN signaling using type I IFN receptor neutralizing antibody significantly reduced immune system activation, decreased expression of IL-10 and PD-L1, restored lymphoid architecture and resurrected lost T cell function. IFN-I blockade both prior to and following establishment of persistent virus infection was associated with virus clearance and was CD4 T cell dependent. Thus, small molecule blockade of the IFN-I signaling pathway may be a viable option to explore as a target to control persistent infections. Study supported by NIH grants AI009484 and U 54 AI057160, and performed by postdoctoral fellows J. Teijaro, C. Ng, B. Sullivan, and with collaborators J.C. de la Torre and R. Schreiber.