Type I interferon (IFN-I) is the first line of mammalian host defense against viral infection. To counteract this, the flaviviruses, like other viruses, have encoded a variety of antagonists, and use a multi-layered molecular defense strategy to establish their infections. Among the most potent antagonists is non-structural protein 5 (NS5), which has been shown for all disease-causing flaviviruses to target different steps and players of the type I IFN signaling pathway. Here, we summarize the type I IFN antagonist mechanisms used by flaviviruses with a focus on the role of NS5 in regulating one key regulator of type I IFN, signal transducer and activator of transcription 2 (STAT2).
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http://dx.doi.org/10.3390/v10120712 | DOI Listing |
J Virol
January 2025
Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.
Unlabelled: SARS-CoV-2 infection induces interferon (IFN) response by plasmacytoid dendritic cells (pDCs), but the underlying mechanisms are poorly defined. Here, we show that the bulk of the IFN-I release comes from pDC sensing of infected cells and not cell-free virions. Physical contact (or conjugates) between pDCs and infected cells is mediated through CD54-CD11a engagement, and such conjugate formation is required for efficient IFN-I production.
View Article and Find Full Text PDFArthritis Rheumatol
January 2025
Division of Rheumatology, Department of Medicine.
Objective: Photosensitivity occurs in ~75% of lupus patients. Although ultraviolet light radiation (UVR) stimulates Type I interferon (IFN-I) in the skin, how UVR induced skin inflammation leads to downstream effects is poorly understood. Tissue inflammation causes DC to migrate from organs to draining lymph nodes (dLN) including a recently identified inflammatory DC subset (inf cDC2) that are potent antigen presenting cells.
View Article and Find Full Text PDFAllergol Int
January 2025
Research Division, Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany; Department of Dermatology and Allergy, University Hospital Aachen, Aachen, Germany.
Background: The detection of drug-specific activation of T cells in the lymphocyte transformation test (LTT) is mainly based on cell proliferation or cytokine secretion. However, the LTT presents with a varying sensitivity and specificity. The aim of our study was to analyse the genome wide gene expression of PBMC to identify drug allergy-specific gene regulation patterns.
View Article and Find Full Text PDFRedox Biol
January 2025
Department of Pathogenic Biology, Key Laboratory of Infection and Immunity of Shandong Province, and Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. Electronic address:
Cellular microenvironments critically control the activation of innate immune responses. N-chlorotaurine (Tau-Cl) is an endogenous metabolite that is markedly produced and secreted during pathogenic invasion. However, its effect on the antiviral innate immune responses remains unclear.
View Article and Find Full Text PDFLancet
January 2025
Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:
Background: Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.
Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 25 university-based hospitals and outpatient sites in Germany, Hungary, Poland, Spain, and the USA.
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