Persistent LCMV Infection Is Controlled by Blockade of Type I Interferon Signaling

• Published in: Science (American Association for the Advancement of Science) 2013-04, Vol.340 (6129), p.207-211
• Main Authors: Teijaro, John R., Ng, Cherie, Lee, Andrew M., Sullivan, Brian M., Sheehan, Kathleen C. F., Welch, Megan, Schreiber, Robert D., de la Torre, Juan Carlos, Oldstone, Michael B. A.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Viral - blood; Arenaviridae Infections - immunology; Arenaviridae Infections - pathology; Arenaviridae Infections - virology; B7-H1 Antigen - metabolism; Blocking; CD4-Positive T-Lymphocytes - immunology; chronic diseases; Chronic illnesses; Cytokines - metabolism; Dendritic Cells - immunology; Dendritic Cells - virology; Female; Hepatitis C virus; HIV; Human; human diseases; Human immunodeficiency virus; immune response; Immune system; Immune Tolerance; Interferon; Interferon Type I - immunology; Interferon Type I - metabolism; interferons; Interleukin-10 - metabolism; lymphatic system; Lymphocytes - immunology; Lymphocytes - virology; Lymphocytic choriomeningitis mammarenavirus; Lymphocytic choriomeningitis virus - immunology; Lymphocytic choriomeningitis virus - physiology; Male; Mice; Mice, Inbred C57BL; Organs; Receptor, Interferon alpha-beta - immunology; Receptor, Interferon alpha-beta - metabolism; Signal Transduction; Spleen - immunology; Spleen - pathology; Viral infections; viral load; Viremia; Viruses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1235214

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.