title: Blockade of chronic type I interferon signaling to control persistent LCMV infection.
abstract: 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.
authors.affiliation: 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 90095, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Wilson
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Yamada
authors.forename: Heidi
authors.initials: H
authors.lastname: Elsaesser
authors.forename: Jonathan
authors.initials: J
authors.lastname: Herskovitz
authors.forename: Jane
authors.initials: J
authors.lastname: Deng
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Karp
authors.forename: David G
authors.initials: DG
authors.lastname: Brooks
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001117:Arenaviridae Infections / Q000276:immunology* / Q000821:virology*; D060890:B7-H1 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D020869:Gene Expression Profiling; D007108:Immune Tolerance; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000502:physiology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D053633:Receptor, Interferon alpha-beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014779:Virus Replication
chemical_list: D000906:Antibodies; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D016207:Cytokines; C556062:IL10 protein, mouse; C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D016753:Interleukin-10; D053633:Receptor, Interferon alpha-beta; D007371:Interferon-gamma