Modulation of type I interferon responses potently inhibits SARS-CoV-2 replication and inflammation in rhesus macaques.

Autor: Viox EG; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Hoang TN; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Upadhyay AA; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Nchioua R; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany., Hirschenberger M; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany., Strongin Z; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Tharp GK; Emory NPRC Genomics Core Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Pino M; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Nguyen K; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Harper JL; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Gagne M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Marciano S; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel., Boddapati AK; Emory NPRC Genomics Core Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Pellegrini KL; Emory NPRC Genomics Core Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Pradhan A; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Tisoncik-Go J; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA., Whitmore LS; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA., Karunakaran KA; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Roy M; Division of Pathology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Kirejczyk S; StageBio, 5930 Main St., Mount Jackson, VA 22842, USA., Curran EH; Division of Pathology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Wallace C; Division of Animal Resources, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Wood JS; Division of Animal Resources, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Connor-Stroud F; Division of Animal Resources, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Voigt EA; RNA Vaccines Group, Access to Advanced Health Institute, Seattle, WA 98102, USA., Monaco CM; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA., Gordon DE; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA., Kasturi SP; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA., Levit RD; Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA., Gale M Jr; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA., Vanderford TH; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA., Silvestri G; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA., Busman-Sahay K; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA., Estes JD; Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR 97006, USA.; Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.; Department of Clinical Medicine, Aarhus University, Aarhus 8000, Denmark.; School of Health and Biomedical Sciences, College of Science, Engineering and Health, RMIT University, Melbourne, VIC 3000, Australia., Vaccari M; Division of Immunology, Tulane National Primate Research Center, Covington, LA 70433, USA.; Department of Microbiology and Immunology, Tulane School of Medicine, New Orleans, LA 70112, USA., Douek DC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Sparrer KMJ; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany., Johnson RP; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Infectious Disease Division, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Kirchhoff F; Institute of Molecular Virology, Ulm University Medical Center, 89081 Ulm, Germany., Schreiber G; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 76100, Israel., Bosinger SE; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Emory NPRC Genomics Core Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA., Paiardini M; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2023 Jul 28; Vol. 8 (85), pp. eadg0033. Date of Electronic Publication: 2023 Jul 28.
DOI: 10.1126/sciimmunol.adg0033
Abstrakt: Type I interferons (IFN-I) are critical mediators of innate control of viral infections but also drive the recruitment of inflammatory cells to sites of infection, a key feature of severe coronavirus disease 2019. Here, IFN-I signaling was modulated in rhesus macaques (RMs) before and during acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection using a mutated IFN-α2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous IFN-I. IFNmod treatment in uninfected RMs was observed to induce a modest up-regulation of only antiviral IFN-stimulated genes (ISGs); however, in SARS-CoV-2-infected RMs, IFNmod reduced both antiviral and inflammatory ISGs. IFNmod treatment resulted in a potent reduction in SARS-CoV-2 viral loads both in vitro in Calu-3 cells and in vivo in bronchoalveolar lavage (BAL), upper airways, lung, and hilar lymph nodes of RMs. Furthermore, in SARS-CoV-2-infected RMs, IFNmod treatment potently reduced inflammatory cytokines, chemokines, and CD163 + MRC1 - inflammatory macrophages in BAL and expression of Siglec-1 on circulating monocytes. In the lung, IFNmod also reduced pathogenesis and attenuated pathways of inflammasome activation and stress response during acute SARS-CoV-2 infection. Using an intervention targeting both IFN-α and IFN-β pathways, this study shows that, whereas early IFN-I restrains SARS-CoV-2 replication, uncontrolled IFN-I signaling critically contributes to SARS-CoV-2 inflammation and pathogenesis in the moderate disease model of RMs.
Databáze: MEDLINE