Journal ArticleDOI
Functional role of type I and type II interferons in antiviral defense.
Ulrike Müller,Ulrich Steinhoff,Luiz F. L. Reis,Silvio Hemmi,Jovan Pavlovic,Rolf M. Zinkernagel,Michel Aguet +6 more
TLDR
Comparison of mice lacking either type I or type II IFN receptors showed that, at least in response to some viruses, both IFN systems are essential for antiviral defense and are functionally nonredundant.Abstract:
Mice lacking the known subunit of the type I interferon (IFN) receptor were completely unresponsive to type I IFNs, suggesting that this receptor chain is essential for type I IFN-mediated signal transduction. These mice showed no overt anomalies but were unable to cope with viral infections, despite otherwise normal immune responses. Comparison of mice lacking either type I or type II IFN receptors showed that, at least in response to some viruses, both IFN systems are essential for antiviral defense and are functionally nonredundant.read more
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Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality in SARS-CoV-2 infection and cytokine shock syndromes
Rajendra Karki,Bhesh Raj Sharma,Shraddha Tuladhar,Evan P. Williams,Lillian Zalduondo,Parimal Samir,Min Zheng,Balamurugan Sundaram,Balaji Banoth,R. K. Subbarao Malireddi,Patrick Schreiner,Geoffrey Neale,Peter Vogel,Richard Webby,Colleen B. Jonsson,Thirumala-Devi Kanneganti +15 more
TL;DR: In vivo neutralization of both TNF-α and IFN-γ in multiple disease models associated with cytokine storm showed that this treatment provided substantial protection against not only SARS-CoV-2 infection, but also sepsis, hemophagocytic lymphohistiocytosis, and cytokine shock models, demonstrating the broad physiological relevance of this mechanism.
Journal ArticleDOI
Activation of Pattern Recognition Receptor-Mediated Innate Immunity Inhibits the Replication of Hepatitis B Virus in Human Hepatocyte-Derived Cells
Haitao Guo,Dong Jiang,Dongling Ma,Jinhong Chang,Anne Marie Dougherty,Andrea Cuconati,Timothy M. Block,Ju-Tao Guo +7 more
TL;DR: The results suggest that besides NF-κB, additional signaling pathway(s) are required for TRIF to induce a maximum antiviral response against HBV, and that knowing the molecular mechanisms by which PRR-mediated innate defense responses control HBV infections could potentially lead to the development of novel therapeutics.
Journal ArticleDOI
The type-I interferon receptor. The long and short of it.
TL;DR: New advances in the production of specific monoclonal antibodies against the receptor and the cloning of different receptor subunits are analyzed and the role of the different receptors subunits in type-I interferon signaling is analyzed.
Journal ArticleDOI
IFN-α Enhances Peptide Vaccine-Induced CD8+ T Cell Numbers, Effector Function, and Antitumor Activity
Andrew G. Sikora,Nina Jaffarzad,Yared Hailemichael,Alexander Gelbard,Alexander Gelbard,Spencer W. Stonier,Kimberly S. Schluns,Loredana Frasca,Yanyan Lou,Chengwen Liu,Helen A. Andersson,Patrick Hwu,Willem W. Overwijk +12 more
TL;DR: The efficacy and mechanism of exogenous IFN-α as an adjuvant for peptide vaccination are demonstrated, insight is given into its mechanism of action, and a rationale for clinical trials in which vaccination is combined with standard-of-care IFn-α therapy for melanoma is provided.
Journal ArticleDOI
Tristetraprolin Mediates Interferon-γ mRNA Decay
Rachel L. Ogilvie,Julius R. SternJohn,Bernd Rattenbacher,Irina A. Vlasova,Darlisha A. Williams,Heidi H. Hau,Perry J. Blackshear,Paul R. Bohjanen +7 more
TL;DR: Results suggest that TTP binds to a functional AU-rich element in the 3′-untranslated region of IFN-γ mRNA and mediates rapid degradation of the IFn-γ transcript.
References
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Journal ArticleDOI
Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family
TL;DR: This sequence allowed the determination of the hitherto unknown primary structure of rat GAPDH which is 333 aminoacids long and revealed a high degree of sequence conservation at both nucleotide and protein levels.
Journal ArticleDOI
Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes
TL;DR: A positive and negative selection procedure is described that enriches 2,000-fold for those cells that contain a targeted mutation in mouse embryo-derived stem cells.
Journal ArticleDOI
Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein
Hansruedi Büeler,Marek Fischer,Yolande Lang,Yolande Lang,Horst Bluethmann,Horst Bluethmann,Hans-Peter Lipp,Stephen J. DeArmond,Stephen J. DeArmond,Stanley B. Prusiner,Stanley B. Prusiner,Michel Aguet,Charles Weissmann +12 more
TL;DR: It is now feasible to determine whether mice devoid of PrPc can propagate prions and are susceptible to scrapie pathogenesis.
Journal ArticleDOI
Immune response in mice that lack the interferon-gamma receptor.
Sui Huang,Wiljan Hendriks,Alana Althage,Silvio Hemmi,Horst Bluethmann,Ryutaro Kamijo,Jan Vilcek,Rolf M. Zinkernagel,Michel Aguet +8 more
TL;DR: Mutant mice offer the possibility for the further elucidation of IFN-gamma-mediated functions by transgenic cell- or tissue-specific reconstitution of a functional receptor.
Journal ArticleDOI
Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-β gene regulatory elements
Masaaki Miyamoto,Takashi Fujita,Yoko Kimura,Mitsuo Maruyama,Hisashi Harada,Yoshiaki Sudo,Takashi Miyata,Tadatsugu Taniguchi +7 more
TL;DR: It is shown here that the IRF-1 gene possesses virus-inducible promoter and is also involved in the regulation of other genes such as IFN-alpha and MHC class I genes.