Treatments that block interferon signaling may help control persistent viral infections. Interferon is the body's major first line of defense against viral infection. Paradoxically, interferon signaling surpresses the immune system in ways that promote persistent infection. Keep an eye on this as interferon has interested ME/CFS researchers for over 20 years, Ampligen is an interferon inducer, & Klimas/Broderick are currently looking at it among other things... Two high-profile animal model studies in Science 12 April 2013 involving numerous NIH grants: Persistent LCMV infection is controlled by blockade of type I interferon signaling Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA , USA. During persistent viral infections, chronic immune activation, negative immune regulator expression, an elevated interferon signature, and lymphoid tissue destruction correlate with disease progression. We demonstrated that blockade of type I interferon (IFN-I) signaling using an IFN-I receptor neutralizing antibody reduced immune system activation, decreased expression of negative immune regulatory molecules, and restored lymphoid architecture in mice persistently infected with lymphocytic choriomeningitis virus. IFN-I blockade before and after establishment of persistent virus infection resulted in enhanced virus clearance and was CD4 T cell-dependent. Hence, we demonstrate a direct causal link between IFN-I signaling, immune activation, negative immune regulator expression, lymphoid tissue disorganization, and virus persistence. Our results suggest that therapies targeting IFN-I may help control persistent virus infections. Blockade of chronic type I interferon signaling to control persistent LCMV infection. Department of Microbiology, Immunology and Molecular Genetics and the UCLA AIDS Institute, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA , USA. Type I interferons (IFN-I) are critical for antiviral immunity; however, chronic IFN-I signaling is associated with hyperimmune activation and disease progression in persistent infections. We demonstrated in mice that blockade of IFN-I signaling diminished chronic immune activation and immune suppression, restored lymphoid tissue architecture, and increased immune parameters associated with control of virus replication, ultimately facilitating clearance of the persistent infection. The accelerated control of persistent infection induced by blocking IFN-I signaling required CD4 T cells and was associated with enhanced IFN-γ production. Thus, we demonstrated that interfering with chronic IFN-I signaling during persistent infection redirects the immune environment to enable control of infection.