title: Persistent LCMV infection is controlled by blockade of type I interferon signaling.
abstract: 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.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Teijaro
authors.forename: Cherie
authors.initials: C
authors.lastname: Ng
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lee
authors.forename: Brian M
authors.initials: BM
authors.lastname: Sullivan
authors.forename: Kathleen C F
authors.initials: KC
authors.lastname: Sheehan
authors.forename: Megan
authors.initials: M
authors.lastname: Welch
authors.forename: Robert D
authors.initials: RD
authors.lastname: Schreiber
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: de la Torre
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001117:Arenaviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D060890:B7-H1 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005260:Female; D007108:Immune Tolerance; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053633:Receptor, Interferon alpha-beta / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014766:Viremia
chemical_list: D000914:Antibodies, Viral; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D016207:Cytokines; C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D016753:Interleukin-10; D053633:Receptor, Interferon alpha-beta