scholarly journals Nicastrin haploinsufficiency alters expression of type I interferon‐stimulated genes: the relationship to familial hidradenitis suppurativa

2019 ◽  
Vol 44 (4) ◽  
pp. e118-e125 ◽  
Author(s):  
L. Cao ◽  
D. J. Morales‐Heil ◽  
E. D. O. Roberson
Keyword(s):  
Hidradenitis Suppurativa ◽  
Type I Interferon ◽  
Type I ◽  
Interferon Stimulated Genes ◽  
The Relationship

scholarly journals Positive natural selection in primate genes of the type I interferon response

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elena N. Judd ◽  
Alison R. Gilchrist ◽  
Nicholas R. Meyerson ◽  
Sara L. Sawyer
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Multiple Sequence Alignments ◽  
Interferon Stimulated Genes ◽  
Interferon Induction

Abstract Background The Type I interferon response is an important first-line defense against viruses. In turn, viruses antagonize (i.e., degrade, mis-localize, etc.) many proteins in interferon pathways. Thus, hosts and viruses are locked in an evolutionary arms race for dominance of the Type I interferon pathway. As a result, many genes in interferon pathways have experienced positive natural selection in favor of new allelic forms that can better recognize viruses or escape viral antagonists. Here, we performed a holistic analysis of selective pressures acting on genes in the Type I interferon family. We initially hypothesized that the genes responsible for inducing the production of interferon would be antagonized more heavily by viruses than genes that are turned on as a result of interferon. Our logic was that viruses would have greater effect if they worked upstream of the production of interferon molecules because, once interferon is produced, hundreds of interferon-stimulated proteins would activate and the virus would need to counteract them one-by-one. Results We curated multiple sequence alignments of primate orthologs for 131 genes active in interferon production and signaling (herein, “induction” genes), 100 interferon-stimulated genes, and 100 randomly chosen genes. We analyzed each multiple sequence alignment for the signatures of recurrent positive selection. Counter to our hypothesis, we found the interferon-stimulated genes, and not interferon induction genes, are evolving significantly more rapidly than a random set of genes. Interferon induction genes evolve in a way that is indistinguishable from a matched set of random genes (22% and 18% of genes bear signatures of positive selection, respectively). In contrast, interferon-stimulated genes evolve differently, with 33% of genes evolving under positive selection and containing a significantly higher fraction of codons that have experienced selection for recurrent replacement of the encoded amino acid. Conclusion Viruses may antagonize individual products of the interferon response more often than trying to neutralize the system altogether.

scholarly journals An Easy and Reliable Strategy for Making Type I Interferon Signature Analysis Comparable among Research Centers

Diagnostics ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 113 ◽  
Author(s):  
Alessia Pin ◽  
Lorenzo Monasta ◽  
Andrea Taddio ◽  
Elisa Piscianz ◽  
Alberto Tommasini ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Type I Interferon ◽  
Diagnostic Value ◽  
Type I ◽  
Data Normalization ◽  
Signature Analysis ◽  
Interferon Signature ◽  
Interferon Stimulated Genes ◽  
Targeted Treatments ◽  
To Receive

Interferon-stimulated genes (ISGs) are a set of genes whose transcription is induced by interferon (IFN). The measure of the expression of ISGs enables calculating an IFN score, which gives an indirect estimate of the exposition of cells to IFN-mediated inflammation. The measure of the IFN score is proposed for the screening of monogenic interferonopathies, like the Aicardi-Goutières syndrome, or to stratify subjects with systemic lupus erythematosus to receive IFN-targeted treatments. Apart from these scenarios, there is no agreement on the diagnostic value of the score in distinguishing IFN-related disorders from diseases dominated by other types of cytokines. Since the IFN score is currently measured in several research hospitals, merging experiences could help define the potential of scoring IFN inflammation in clinical practice. However, the IFN score calculated at different laboratories may be hardly comparable due to the distinct sets of IFN-stimulated genes assessed and to different controls used for data normalization. We developed a reliable approach to minimize the inter-laboratory variability, thereby providing shared strategies for the IFN signature analysis and allowing different centers to compare data and merge their experiences.

Intrahepatic mRNA Levels of Type I Interferon Receptor and Interferon-Stimulated Genes in Genotype 1b Chronic Hepatitis C

Intervirology ◽  
2006 ◽  
Vol 50 (1) ◽  
pp. 32-39 ◽  
Author(s):  
Hideaki Taniguchi ◽  
Yoshiaki Iwasaki ◽  
Akira Takahashi ◽  
Hiroyuki Shimomura ◽  
Akio Moriya ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Type I Interferon ◽  
Type I ◽  
Mrna Levels ◽  
Interferon Stimulated Genes ◽  
Genotype 1B ◽  
Interferon Receptor

Double-stranded RNA induces the expression of type I interferon-stimulated genes 54 and 56 in human astrocyte cell line

2014 ◽  
Vol 275 (1-2) ◽  
pp. 94
Author(s):  
Fei Xing ◽  
Tomoh Matsumiya ◽  
Ryo Hayakari ◽  
Hidemi Yoshida ◽  
Tadaatsu Imaizumi
Keyword(s):  
Cell Line ◽  
Type I Interferon ◽  
Type I ◽  
Double Stranded Rna ◽  
Human Astrocyte ◽  
Interferon Stimulated Genes

scholarly journals IFN-β, but not IFN-α, is Responsible for the Pro-Bacterial Effect of Type I Interferon

2021 ◽  
Vol 55 (3) ◽  
pp. 256-264
Keyword(s):  
Dendritic Cells ◽  
Bacterial Infections ◽  
Type I Interferon ◽  
Cytotoxic T Cells ◽  
Type I ◽  
Interferon Stimulated Genes ◽  
Common Receptor ◽  
Wide Range ◽  
Blocking Antibodies ◽  
Bacterial Effect

BACKGROUND/AIMS: During an immune response, type I interferon (IFN-I) signaling induces a wide range of changes, including those which are required to overcome viral infection and those which suppress cytotoxic T cells to avoid immunopathology. During certain bacterial infections, IFN-I signaling exerts largely detrimental effects. Although the IFN-I family of proteins all share one common receptor, biologic responses to signaling vary depending on IFN-I subtype. Here, we asked if one IFN-I subtype dominates the pro-bacterial effect of IFN-I signaling and found that control of Listeria monocytogenes (L.m.) infection is more strongly suppressed by IFN-β than IFN-α. METHODS: To study this, we measured bacterial titers in IFNAR-/-, IFN-β‑/‑, Stat2-/-, Usp18fl/fl and Usp18fl/fl x CD11c-Cre mice models in addition to IFN-I blocking antibodies. Moreover, we measured interferon stimulated genes in bone marrow derived dendritic cells after treatment with IFN-α4 and IFN-β. RESULTS: Specifically, we show that genetic deletion of IFN-β or antibody-mediated IFN-β neutralization was sufficient to reduce bacterial titers to levels similar to those observed in mice that completely lack IFN-I signaling (IFNAR-/- mice). However, IFN-α blockade failed to significantly reduce L.m. titers, suggesting that IFN-β is the dominant IFN-I subtype responsible for the pro-bacterial effect of IFN-I. Mechanistically, when focusing on IFN-I signals to dendritic cells, we found that IFN-β induces ISGs more robustly than IFN-α, including USP18, the protein we previously identified as driving the pro-bacterial effects of IFN-I. Further, we found that this induction was STAT1/STAT2 heterodimer- or STAT2/STAT2 homodimer-dependent, as STAT2-deficient mice were more resistant to L.m. infection. CONCLUSION: In conclusion, IFN-Β is the principal member of the IFN-I family responsible for driving the pro-bacterial effect of IFN-I.

scholarly journals Mechanisms of type I interferon action and its role in infections and diseases transmission in mammals

2017 ◽  
Vol 64 (2) ◽  
Author(s):  
Weronika Ratajczak ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Beata Tokarz-Deptuła ◽  
Wiesław Deptuła
Keyword(s):  
Signaling Pathways ◽  
Crucial Role ◽  
Viral Infections ◽  
Type I Interferon ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Stimulated Genes

Interferons (IFN) are pivotal regulators of immunological processes. The paper describes mainly type I interferons -α and –β and its recently recounted signaling pathways, especially ISG – interferon stimulated genes, having a crucial role in regulating IFN recruitment. Moreover, the paper shows the data on the role of interferons -α and –β in infections – not only commonly known viral infections, but also bacterial, fungal and parasitic. 

scholarly journals The HUSH complex is a gatekeeper of type I interferon through epigenetic regulation of LINE-1s

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Hale Tunbak ◽  
Rocio Enriquez-Gasca ◽  
Christopher H. C. Tie ◽  
Poppy A. Gould ◽  
Petra Mlcochova ◽  
...  
Keyword(s):  
Dna Damage ◽  
Type I Interferon ◽  
Type I ◽  
Human Cell Lines ◽  
Interferon Signaling ◽  
Interferon Stimulated Genes ◽  
Primary Fibroblasts ◽  
Gene Regulatory ◽  
Epigenetic Repression ◽  
Specific Line

Abstract The Human Silencing Hub (HUSH) complex is necessary for epigenetic repression of LINE-1 elements. We show that HUSH-depletion in human cell lines and primary fibroblasts leads to induction of interferon-stimulated genes (ISGs) through JAK/STAT signaling. This effect is mainly attributed to MDA5 and RIG-I sensing of double-stranded RNAs (dsRNAs). This coincides with upregulation of primate-conserved LINE-1s, as well as increased expression of full-length hominid-specific LINE-1s that produce bidirectional RNAs, which may form dsRNA. Notably, LTRs nearby ISGs are derepressed likely rendering these genes more responsive to interferon. LINE-1 shRNAs can abrogate the HUSH-dependent response, while overexpression of an engineered LINE-1 construct activates interferon signaling. Finally, we show that the HUSH component, MPP8 is frequently downregulated in diverse cancers and that its depletion leads to DNA damage. These results suggest that LINE-1s may drive physiological or autoinflammatory responses through dsRNA sensing and gene-regulatory roles and are controlled by the HUSH complex.

scholarly journals Transcriptomic Analysis Reveals a Mechanism for a Prefibrotic Phenotype in STAT1 Knockout Mice during Severe Acute Respiratory Syndrome Coronavirus Infection

2010 ◽  
Vol 84 (21) ◽  
pp. 11297-11309 ◽  
Author(s):  
Gregory A. Zornetzer ◽  
Matthew B. Frieman ◽  
Elizabeth Rosenzweig ◽  
Marcus J. Korth ◽  
Carly Page ◽  
...  
Keyword(s):  
T Cell ◽  
Severe Acute Respiratory Syndrome ◽  
Type I Interferon ◽  
Transcriptional Response ◽  
Specific Gene ◽  
Type I ◽  
Alternatively Activated Macrophages ◽  
Interferon Stimulated Genes ◽  
Interferon Receptor ◽  
End Stage

ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV) infection can cause the development of severe end-stage lung disease characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. The mechanisms by which pulmonary lesions and fibrosis are generated during SARS-CoV infection are not known. Using high-throughput mRNA profiling, we examined the transcriptional response of wild-type (WT), type I interferon receptor knockout (IFNAR1−/−), and STAT1 knockout (STAT1−/−) mice infected with a recombinant mouse-adapted SARS-CoV (rMA15) to better understand the contribution of specific gene expression changes to disease progression. Despite a deletion of the type I interferon receptor, strong expression of interferon-stimulated genes was observed in the lungs of IFNAR1−/− mice, contributing to clearance of the virus. In contrast, STAT1−/− mice exhibited a defect in the expression of interferon-stimulated genes and were unable to clear the infection, resulting in a lethal outcome. STAT1−/− mice exhibited dysregulation of T-cell and macrophage differentiation, leading to a TH2-biased immune response and the development of alternatively activated macrophages that mediate a profibrotic environment within the lung. We propose that a combination of impaired viral clearance and T-cell/macrophage dysregulation causes the formation of prefibrotic lesions in the lungs of rMA15-infected STAT1−/− mice.

scholarly journals The relationship between the type I interferon signature and the response to rituximab in rheumatoid arthritis

2010 ◽  
Vol 69 (Suppl 2) ◽  
pp. A14-A15
Author(s):  
R M Thurlings ◽  
M Boumans ◽  
J Tekstra ◽  
K Vos ◽  
D M van Westing ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Type I Interferon ◽  
Type I ◽  
Interferon Signature ◽  
The Relationship
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