Viral pandemics pose great threats to human health and the economy. The host evolved a complex immune response against viral infection. Matrix metalloproteinase 3 (MMP3), also known as stromelysin-1, has an emerging role in immune regulation during pathogen infection. Using in vitro and in vivo infection models, we showed that MMP3 exhibits broad-spectrum antiviral activities against vesicular stomatitis virus (VSV), influenza A virus (H1N1) and human herpes virus 1 (HSV-1). MMP3 deficient mice are susceptible to viral infection and display a compromised antiviral immune response. Correspondingly, the mice with MMP3 overexpression are resistant to viral infection. The mechanistic study suggested that MMP3 is translocated from the cytoplasm into the cell nucleus upon virus infection and influence NF-κB activities, thus amplifying antiviral immune responses. This study suggested a novel function of MMP3 in viral infection and provided new ideas for developing antiviral drugs based on modulating MMP activity.
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http://dx.doi.org/10.1016/j.antiviral.2022.105388 | DOI Listing |
Neurobiol Dis
January 2025
Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, FL 32611, USA.
Abnormal tau phosphorylation is a key mechanism in neurodegenerative diseases. Evidence implicates infectious agents, such as Herpes Simplex Virus 1 (HSV-1), as co-factors in the onset or the progression of neurodegenerative diseases, including Alzheimer's disease. This has led to divergence in the field regarding the contribution of viruses in the etiology of neurodegenerative diseases.
View Article and Find Full Text PDFMech Ageing Dev
January 2025
San Raffaele University; Department of Human Sciences and Promotion of the Quality of Life, Via di Val Cannuta 247, 00166 Rome, Italy; Clinical and Molecular Epidemiology, IRCCS San Raffaele Roma, Via di Val Cannuta 247, 00166 Rome, Italy. Electronic address:
Introduction: Torque Teno Virus (TTV), an "orphan" virus with unclear pathology, has been associated with various diseases and immune dysfunctions. This study investigates the link between TTV viremia and clinical markers in patients with severe to very severe COPD undergoing respiratory rehabilitation.
Methods: We analyzed 102 elderly COPD patients, stratified by TTV viremia levels (< or ≥ 4 log10 copies/mL).
Immunity
January 2025
Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent's Clinical School, UNSW Sydney, Sydney, NSW, Australia. Electronic address:
The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive the accumulation of a large disease-causing clone. A method for quantifying low-affinity binding revealed recurring antibody variable domain combinations created by V(D)J recombination that bound self-immunoglobulin G (IgG) but not viral E2 antigen.
View Article and Find Full Text PDFCell Host Microbe
January 2025
Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. Electronic address:
Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species.
View Article and Find Full Text PDFCell Stem Cell
January 2025
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn-Children's Hospital of Philadelphia Lung Biology Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:
Functional regeneration of the lung's gas exchange surface following injury requires the coordination of a complex series of cell behaviors within the alveolar niche. Using single-cell transcriptomics combined with lineage tracing of proliferating progenitors, we examined mouse lung regeneration after influenza injury, demonstrating an asynchronously phased response across different cellular compartments. This longitudinal atlas of injury responses has produced a catalog of transient and persistent transcriptional alterations in cells as they transit across axes of differentiation.
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