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 The Robust Restriction of Zika Virus by Type-I Interferon in A549 Cells Varies by Viral Lineage and Is Not Determined by IFITM3

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 503 ◽  
Author(s):  
Theodore A. Gobillot ◽  
Daryl Humes ◽  
Amit Sharma ◽  
Caroline Kikawa ◽  
Julie Overbaugh
Keyword(s):  
Cell Line ◽  
Zika Virus ◽  
Type I Interferon ◽  
A549 Cells ◽  
Antiviral Effect ◽  
Type I ◽  
Zikv Infection ◽  
Interferon Stimulated Genes ◽  
Fold Reduction ◽  
Viral Lineage

Type-I interferon (IFN-I) is a major antiviral host response but its impact on Zika virus (ZIKV) replication is not well defined, particularly as it relates to different circulating strains. Interferon stimulated genes (ISGs) that inhibit ZIKV, such as IFITM3, have been identified largely using overexpression studies. Here, we tested whether diverse ZIKV strains differed in their susceptibility to IFN-I-mediated restriction and the contribution of IFITM3 to this restriction. We identified a robust IFN-I-mediated antiviral effect on ZIKV replication (>100-fold reduction) in A549 cells, a commonly used cell line to study ZIKV replication. The extent of inhibition depended on the IFN-I type and the virus strain tested. Viruses from the American pathogenic outbreak were more sensitive to IFNα (p = 0.049) and IFNβ (p = 0.09) than African-lineage strains, which have not been linked to severe pathogenesis. Knocking out IFITM3 expression did not dampen the IFN-I antiviral effect and only high overexpression of IFITM3 led to ZIKV inhibition. Moreover, IFITM3 expression levels in different cells were not associated with IFN-mediated ZIKV inhibition. Taken together, our findings indicate that there is a robust IFN-I-mediated antiviral effect on ZIKV infection, particularly for American viruses, that is not due to IFITM3. A549 cells, which are a commonly used cell line to study ZIKV replication, present an opportunity for the discovery of novel antiviral ISGs against ZIKV.

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.

Epigenetic regulation of frog innate immunity: Discovery of frog microRNAs associated with antiviral responses and ranavirus infection using a Xenopus laevis skin epithelial-like cell line

2021 ◽  
Author(s):  
Lauren A. Todd ◽  
Maxwell P. Bui-Marinos ◽  
Barbara A. Katzenback
Keyword(s):  
Xenopus Laevis ◽  
Cell Line ◽  
Antiviral Immunity ◽  
Type I Interferons ◽  
Poly I:C ◽  
Type I ◽  
Frog Virus ◽  
Interferon Stimulated Genes ◽  
Antiviral Responses ◽  
Innate Antiviral Immunity

Epigenetic regulators such as microRNAs are emerging as conserved regulators of innate antiviral immunity in vertebrates, yet their roles in amphibian antiviral responses remain uncharacterized. We profiled changes in microRNA expressions in the Xenopus laevis skin epithelial–like cell line Xela DS2 in response to poly(I:C) – an analogue of double-stranded viral RNA and inducer of type I interferons – or frog virus 3 (FV3), an immunoevasive virus associated with amphibian mortality events. We sequenced small RNA libraries generated from untreated, poly(I:C)–treated, and FV3–infected cells. We detected 136 known X. laevis microRNAs and discovered 133 novel X. laevis microRNAs. Sixty–five microRNAs were differentially expressed in response to poly(I:C), many of which were predicted to target regulators of antiviral pathways such as cGAS–STING, RIG–I/MDA–5, TLR signaling, and type I interferon signaling, as well as products of these pathways (NF–κB–induced and interferon-stimulated genes). In contrast, only 49 microRNAs were altered by FV3 infection, fewer of which were predicted to interact with antiviral pathways. Interestingly, poly(I:C) treatment or FV3 infection downregulated transcripts encoding factors of the host microRNA biogenesis pathway. Our study is the first to suggest that host microRNAs regulate innate antiviral immunity in frogs, and sheds light on microRNA–mediated mechanisms of immunoevasion by FV3.

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

scholarly journals Inactivation of the type I interferon pathway reveals long double‐stranded RNA ‐mediated RNA interference in mammalian cells

2016 ◽  
Vol 35 (23) ◽  
pp. 2505-2518 ◽  
Author(s):  
Pierre V Maillard ◽  
Annemarthe G Van der Veen ◽  
Safia Deddouche‐Grass ◽  
Neil C Rogers ◽  
Andres Merits ◽  
...  
Keyword(s):  
Rna Interference ◽  
Mammalian Cells ◽  
Type I Interferon ◽  
Type I ◽  
Double Stranded Rna ◽  
Interferon Pathway

scholarly journals Ladder-like amplification of the type I interferon gene cluster in the human osteosarcoma cell line MG63

2008 ◽  
Vol 16 (8) ◽  
pp. 1177-1192 ◽  
Author(s):  
Narasimharao V. Marella ◽  
Michael J. Zeitz ◽  
Kishore S. Malyavantham ◽  
Artem Pliss ◽  
Sei-ichi Matsui ◽  
...  
Keyword(s):  
Cell Line ◽  
Gene Cluster ◽  
Type I Interferon ◽  
Type I ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma Cell Line ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell ◽  
Interferon Gene ◽  
Osteosarcoma Cell Line Mg63

scholarly journals Double-stranded RNA analog and type I interferon regulate expression of Trem paired receptors in murine myeloid cells

2016 ◽  
Vol 17 (1) ◽  
Author(s):  
Jun Kasamatsu ◽  
Mengyao Deng ◽  
Masahiro Azuma ◽  
Kenji Funami ◽  
Hiroaki Shime ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Myeloid Cells ◽  
Type I ◽  
Double Stranded Rna

scholarly journals Editing of the Human TRIM5 Gene to Introduce Mutations with the Potential to Inhibit HIV-1

2017 ◽  
Author(s):  
Caroline Dufour ◽  
Alix Claudel ◽  
Nicolas Joubarne ◽  
Natacha Merindol ◽  
Tara Maisonnet ◽  
...  
Keyword(s):  
Cell Line ◽  
Type I Interferon ◽  
Human Cells ◽  
Restriction Factor ◽  
Type I ◽  
Dna Transfection ◽  
Homology Directed Repair ◽  
Cell Clones ◽  
Overall Efficiency ◽  
Hiv 1

ABSTRACTThe type I interferon (IFN-I)-inducible human restriction factor TRIM5α inhibits the infection of human cells by specific nonhuman retroviruses, such as N-MLV and EIAV, but does not generally target HIV-1. However, the introduction of two aminoacid substitutions, R332G and R355G, in the human TRIM5α (huTRIM5α) domain responsible for retroviral capsid recognition leads to efficient HIV-1 restriction. Using a DNA transfection-based CRISPR-Cas9 genome editing protocol, we successfully mutated TRIM5 to its HIV-1-restrictive version by homology-directed repair (HDR) in HEK293T cells. Nine clones bearing at least one HDR-edited TRIM5 allele containing both mutations were isolated (5.6% overall efficiency), whereas another one contained only the R332G mutation. Of concern, several of these HDR-edited clones contained on-target undesired mutations, and none had all the alleles corrected. We observed a lack of HIV-1 restriction in the cell clones generated, even when cells were stimulated with IFN-I prior to infection. This, however, was partly explained by the unexpectedly low potential for TRIM5α-mediated restriction activity in this cell line. Our study demonstrates the feasibility of editing the TRIM5 gene to in human cells and identifies the main challenges to be addressed in order to use this approach to confer protection from HIV-1.

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