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Single-cell and spatial transcriptomics illuminate bat immunity and barrier tissue evolution.
Mol Biol Evol
January 2025
Shmunis School of Biomedicine and Cancer Research, George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Bats have adapted to pathogens through diverse mechanisms, including increased resistance - rapid pathogen elimination, and tolerance - limiting tissue damage following infection. In the Egyptian fruit bat (an important model in comparative immunology) several mechanisms conferring disease tolerance were discovered, but mechanisms underpinning resistance remain poorly understood. Previous studies on other species suggested that elevated basal expression of innate immune genes may lead to increased resistance to infection.
View Article and Find Full Text PDFDouble-stranded RNA orbivirus disrupts the DNA-sensing cGAS-sting axis to prevent type I IFN induction.
Cell Mol Life Sci
January 2025
Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Consejo Superior de Investigaciones Científicas (CISA-INIA-CSIC), Valdeolmos, Madrid, Spain.
Cyclic GMP-AMP synthase (cGAS) is a DNA sensing cellular receptor that induces IFN-I transcription in response to pathogen and host derived cytosolic DNA and can limit the replication of some RNA viruses. Some viruses have nonetheless evolved mechanisms to antagonize cGAS sensing. In this study, we evaluated the interaction between Bluetongue virus (BTV), the prototypical dsRNA virus of the Orbivirus genus and the Sedoreoviridae family, and cGAS.
View Article and Find Full Text PDFStructural studies of the IFNλ4 receptor complex using cryoEM enabled by protein engineering.
Nat Commun
January 2025
Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA.
IFNλ4 has posed a conundrum in human immunology since its discovery in 2013, with its expression linked to complications with viral clearance. While genetic and cellular studies revealed the detrimental effects of IFNλ4 expression, extensive structural and functional characterization has been limited by the inability to express and purify the protein, complicating explanations of its paradoxical behavior. In this work, we report a method for robust production of IFNλ4.
View Article and Find Full Text PDFAberrant fumarate metabolism links interferon release in diffuse systemic sclerosis.
J Dermatol Sci
January 2025
Biosciences Department, Durham University, Durham, United Kingdom. Electronic address:
Background: Systemic Sclerosis (SSc) is an idiopathic rheumatic inflammatory disease that is characterised by inflammation and skin fibrosis. Type I interferon is significantly elevated in the disease.
Objective: The objective of this study is to determine the role of the TCA cycle metabolite fumarate in SSc.
P300/RNA polymerase II mediates induction of the teleost viral RNA sensor MDA5 through the interferon regulatory factor IRF11.
J Biol Chem
January 2025
State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519000, China. Electronic address:
Melanoma differentiation-associated gene 5 (MDA5) initiates type I interferon (IFN) production by detecting cytosolic viral RNA. Mammalian MDA5 is an IFN-inducible gene and controlled by IFN regulatory factor 1 (IRF1). Teleost MDA5 also induces type I IFN production in response to viruses, yet its regulation remains largely unexplored.
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