scholarly journals Expression of Interferon-γ by a Coronavirus Defective-Interfering RNA Vector and Its Effect on Viral Replication, Spread, and Pathogenicity

Virology ◽  
1997 ◽  
Vol 233 (2) ◽  
pp. 327-338 ◽  
Author(s):  
Xuming Zhang ◽  
David R. Hinton ◽  
Daniel J. Cua ◽  
Stephen A. Stohlman ◽  
Michael M.C. Lai
Keyword(s):  
Viral Replication ◽  
Interferon Γ ◽  
Defective Interfering Rna ◽  
Interfering Rna

scholarly journals GCN2 drives macrophage and MDSC function and immunosuppression in the tumor microenvironment

2019 ◽  
Vol 4 (42) ◽  
pp. eaax8189 ◽  
Author(s):  
Marie Jo Halaby ◽  
Kebria Hezaveh ◽  
Sara Lamorte ◽  
M. Teresa Ciudad ◽  
Andreas Kloetgen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Macrophage Polarization ◽  
Suppressor Cells ◽  
Interferon Γ ◽  
Mass Cytometry ◽  
General Control ◽  
Immune Attack ◽  
Environmental Sensor ◽  
Rna Knockdown ◽  
Interfering Rna

General control nonderepressible 2 (GCN2) is an environmental sensor controlling transcription and translation in response to nutrient availability. Although GCN2 is a putative therapeutic target for immuno-oncology, its role in shaping the immune response to tumors is poorly understood. Here, we used mass cytometry, transcriptomics, and transcription factor–binding analysis to determine the functional impact of GCN2 on the myeloid phenotype and immune responses in melanoma. We found that myeloid-lineage deletion of GCN2 drives a shift in the phenotype of tumor-associated macrophages and myeloid-derived suppressor cells (MDSCs) that promotes antitumor immunity. Time-of-flight mass cytometry (CyTOF) and single-cell RNA sequencing showed that this was due to changes in the immune microenvironment with increased proinflammatory activation of macrophages and MDSCs and interferon-γ expression in intratumoral CD8+ T cells. Mechanistically, GCN2 altered myeloid function by promoting increased translation of the transcription factor CREB-2/ATF4, which was required for maturation and polarization of macrophages and MDSCs in both mice and humans, whereas targeting Atf4 by small interfering RNA knockdown reduced tumor growth. Last, analysis of patients with cutaneous melanoma showed that GCN2-dependent transcriptional signatures correlated with macrophage polarization, T cell infiltrates, and overall survival. Thus, these data reveal a previously unknown dependence of tumors on myeloid GCN2 signals for protection from immune attack.

A defective interfering RNA that contains a mosaic of a plant virus genome

Cell ◽  
1987 ◽  
Vol 51 (3) ◽  
pp. 427-433 ◽  
Author(s):  
Bradley I. Hillman ◽  
James C. Carrington ◽  
Thomas J. Morris
Keyword(s):  
Plant Virus ◽  
Virus Genome ◽  
Defective Interfering Rna ◽  
Interfering Rna

Potentiation of flagellin responses in gut epithelial cells by interferon-γ is associated with STAT-independent regulation of MyD88 expression

2009 ◽  
Vol 423 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Ciara Bannon ◽  
Pam J. Davies ◽  
Andrew Collett ◽  
Geoffrey Warhurst
Keyword(s):  
Epithelial Cells ◽  
Enteric Bacteria ◽  
Interferon Γ ◽  
Janus Kinase ◽  
Cxcl8 Secretion ◽  
Health And Disease ◽  
Toll Like Receptor 5 ◽  
Myeloid Differentiation Factor ◽  
Interfering Rna ◽  
Dose Dependent

Flagellin acting via TLR5 (Toll-like receptor 5) is a key regulator of the host response to the gut microbial flora in both health and disease. The present study has investigated regulation of flagellin–TLR5 signalling in human colonocytes (HT29-19A) by IFNγ (interferon-γ), a cytokine released early in the inflammatory process which has multiple effects on gut epithelial function that may facilitate abnormal responses to enteric bacteria. Flagellin induced a dose-dependent secretion of chemokines CXCL8 and CCL2 in the human colonocyte line, HT29-19A. Exposure to IFNγ did not induce chemokine secretion, but markedly potentiated responses to flagellin, increasing CXL8 gene expression and protein secretion by approx. 4-fold. Potentiation by IFNγ was independent of changes in TLR5 and was associated with a rapid, sustained increase in expression of the downstream adaptor molecule MyD88 (myeloid differentiation factor 88). Knockdown of MyD88 expression using siRNA (small interfering RNA) abolished flagellin-dependent CXCL8 secretion and the potentiating effect of IFNγ. Exposure of non-transformed mouse and human colonocytes to IFNγ also increased MyD88 expression. STAT (signal transducer and activator of transcription) 1 knockdown and use of the broad-spectrum JAK (Janus kinase)-STAT inhibitor AG490 had no effect on IFNγ-mediated up-regulation of MyD88. The findings of the present study suggest that IFNγ sensitizes colonic epithelial cells to bacterial flagellin via a largely STAT-independent up-regulation of MyD88 expression leading to increased secretion of immunomodulatory factors. These results indicate that epithelial responses to flagellin are potentiated by IFNγ, most likely mediated by increased MyD88 expression. The present study adds to our understanding of the spectrum of effects of this cytokine on gut epithelium that may contribute to bacterial-driven inflammation in the gut.

scholarly journals Unexpected complexity in the interference activity of a cloned influenza defective interfering RNA

2017 ◽  
Vol 14 (1) ◽  
Author(s):  
Bo Meng ◽  
Kirsten Bentley ◽  
Anthony C. Marriott ◽  
Paul D. Scott ◽  
Nigel J. Dimmock ◽  
...  
Keyword(s):  
Defective Interfering Rna ◽  
Interfering Rna

scholarly journals Defective Interfering RNA Viruses and the Host-Cell Response

1980 ◽  
pp. 137-192 ◽  
Author(s):  
John J. Holland ◽  
S. Ian T. Kennedy ◽  
Bert L. Semler ◽  
Charlotte L. Jones ◽  
Laurent Roux ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Response ◽  
Rna Viruses ◽  
Host Cell Response ◽  
Defective Interfering Rna ◽  
Interfering Rna

scholarly journals 18S defective interfering RNA of Semliki Forest virus contains a triplicated linear repeat.

1981 ◽  
Vol 78 (9) ◽  
pp. 5353-5357 ◽  
Author(s):  
P. Lehtovaara ◽  
H. Soderlund ◽  
S. Keranen ◽  
R. F. Pettersson ◽  
L. Kaariainen
Keyword(s):  
Semliki Forest Virus ◽  
Defective Interfering Rna ◽  
Interfering Rna
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