scholarly journals Leukocytes and Interferon in the Host Response to Viral Infections II. Enhanced Interferon Response of Leukocytes from Immune Animals

1966 ◽  
Vol 91 (6) ◽  
pp. 2185-2191 ◽  
Author(s):  
Lowell A. Glasgow
Keyword(s):  
Host Response ◽  
Viral Infections ◽  
Interferon Response

scholarly journals 521. Similarities and Differences in Transcriptomic Host Response between SARS-CoV-2 and Other Viral Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S326-S327
Author(s):  
Simone A Thair ◽  
Yudong He ◽  
Yehudit Hasin-Brumshtein ◽  
Suraj Sakaram ◽  
Rushika R Pandya ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Nk Cells ◽  
Pathway Analysis ◽  
Host Response ◽  
Viral Infections ◽  
Cell Types ◽  
Gene Signature ◽  
Gene Signatures ◽  
Similarities And Differences

Abstract Background COVID-19 is a pandemic caused by the SARS-CoV-2 virus that shares and differs in clinical characteristics of known viral infections. Methods We obtained RNAseq profiles of 62 prospectively enrolled COVID-19 patients and 24 healthy controls (HC). We collected 23 independent studies profiling 1,855 blood samples from patients covering six viruses (influenza, RSV, HRV, Ebola, Dengue and SARS-CoV-1). We studied host whole-blood transcriptomic responses in COVID-19 compared to non-COVID-19 viral infections to understand similarities and differences in host response. Gene signature threshold was absolute effect size ≥1, FDR ≤ 0.05%. Results Differential gene expression of COVID-19 vs HC are highly correlated with non-COVID-19 vs HC (r=0.74, p< 0.001). We discovered two gene signatures: COVID-19 vs HC (2002 genes) (COVIDsig) and non-COVID-19 vs HC (635 genes) (nonCOVIDsig). Pathway analysis of over-expressed signature genes in COVIDsig or nonCOVIDsig identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection and cytokine production. Conversely, for under-expressed genes, pathways indicated repression of lymphocyte differentiation and activation (Fig1). Intersecting the two gene signatures found two genes significantly oppositely regulated (ACO1, ATL3). We derived a third gene signature using COCONUT to compare COVID-19 to non-COVID-19 viral infections (416 genes) (Fig2). Pathway analysis did not result in significant enrichment, suggesting identification of novel biology (Fig1). Statistical deconvolution of bulk transcriptomic data found M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells and total B cells changed in the same direction across COVID-19 and non-COVID-19 infections. Cell types that increased in COVID-19 relative to non-COVID-19 were CD56bright NK cells, M2 macrophages and total NK cells. Those that decreased in non-COVID-19 relative to COVID-19 were CD56dim NK cells & memory B cells and eosinophils (Fig3). Figure 1 Figure 2 Figure 3 Conclusion The concordant and discordant responses mapped here provide a window to explore the pathophysiology of COVID-19 vs other viral infections and show clear differences in signaling pathways and cellularity as part of the host response to SARS-CoV-2. Disclosures Simone A. Thair, PhD, Inflammatix, Inc. (Employee, Shareholder) Yudong He, PhD, Inflammatix Inc. (Employee) Yehudit Hasin-Brumshtein, PhD, Inflammatix (Employee, Shareholder) Suraj Sakaram, MS in Biochemistry and Molecular Biology, Inflammatix (Employee, Other Financial or Material Support, stock options) Rushika R. Pandya, MS, Inflammatix Inc. (Employee, Shareholder) David C. Rawling, PhD, Inflammatix Inc. (Employee, Shareholder) Purvesh Khatri, PhD, Inflammatix Inc. (Shareholder) Timothy Sweeney, MD, PHD, Inflammatix, Inc. (Employee, Shareholder)

Autophagy receptor CCDC50 tunes the STING-mediated interferon response in viral infections and autoimmune diseases

2021 ◽  
Vol 18 (10) ◽  
pp. 2358-2371
Author(s):  
Panpan Hou ◽  
Yuxin Lin ◽  
Zibo Li ◽  
Ruiqing Lu ◽  
Yicheng Wang ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Viral Infections ◽  
Interferon Response

scholarly journals Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles

2021 ◽  
Vol 22 (11) ◽  
pp. 5655
Author(s):  
Heather Jackson ◽  
Stephanie Menikou ◽  
Shea Hamilton ◽  
Andrew McArdle ◽  
Chisato Shimizu ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Pathway Analysis ◽  
Host Response ◽  
Viral Infections ◽  
Disease Patient ◽  
Inflammatory Disorder ◽  
Comprehensive Picture ◽  
Clustering And Classification ◽  
Infection And Inflammation ◽  
Proteomic Responses

The aetiology of Kawasaki disease (KD), an acute inflammatory disorder of childhood, remains unknown despite various triggers of KD having been proposed. Host ‘omic profiles offer insights into the host response to infection and inflammation, with the interrogation of multiple ‘omic levels in parallel providing a more comprehensive picture. We used differential abundance analysis, pathway analysis, clustering, and classification techniques to explore whether the host response in KD is more similar to the response to bacterial or viral infections at the transcriptomic and proteomic levels through comparison of ‘omic profiles from children with KD to those with bacterial and viral infections. Pathways activated in patients with KD included those involved in anti-viral and anti-bacterial responses. Unsupervised clustering showed that the majority of KD patients clustered with bacterial patients on both ‘omic levels, whilst application of diagnostic signatures specific for bacterial and viral infections revealed that many transcriptomic KD samples had low probabilities of having bacterial or viral infections, suggesting that KD may be triggered by a different process not typical of either common bacterial or viral infections. Clustering based on the transcriptomic and proteomic responses during KD revealed three clusters of KD patients on both ‘omic levels, suggesting heterogeneity within the inflammatory response during KD. The observed heterogeneity may reflect differences in the host response to a common trigger, or variation dependent on different triggers of the condition.

scholarly journals Knockout of IRF7 Highlights its Modulator Function of Host Response Against Avian Influenza Virus and the Involvement of MAPK and TOR Signaling Pathways in Chicken

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 385
Author(s):  
Tae Hyun Kim ◽  
Colin Kern ◽  
Huaijun Zhou
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Host Response ◽  
Antiviral Response ◽  
Influenza Viruses ◽  
Interferon Response ◽  
Type I

Interferon regulatory factor 7 (IRF7) is known as the master transcription factor of the type I interferon response in mammalian species along with IRF3. Yet birds only have IRF7, while they are missing IRF3, with a smaller repertoire of immune-related genes, which leads to a distinctive immune response in chickens compared to in mammals. In order to understand the functional role of IRF7 in the regulation of the antiviral response against avian influenza virus in chickens, we generated IRF7-/- chicken embryonic fibroblast (DF-1) cell lines and respective controls (IRF7wt) by utilizing the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) system. IRF7 knockout resulted in increased viral titers of low pathogenic avian influenza viruses. Further RNA-sequencing performed on H6N2-infected IRF7-/- and IRF7wt cell lines revealed that the deletion of IRF7 resulted in the significant down-regulation of antiviral effectors and the differential expression of genes in the MAPK (mitogen-activated protein kinase) and mTOR (mechanistic target of rapamycin) signaling pathways. Dynamic gene expression profiling of the host response between the wildtype and IRF7 knockout revealed potential signaling pathways involving AP1 (activator protein 1), NF-κB (nuclear factor kappa B) and inflammatory cytokines that may complement chicken IRF7. Our findings in this study provide novel insights that have not been reported previously, and lay a solid foundation for enhancing our understanding of the host antiviral response against the avian influenza virus in chickens.

scholarly journals Sex-Dependent Intestinal Replication of an Enteric Virus

2017 ◽  
Vol 91 (7) ◽  
Author(s):  
Christopher M. Robinson ◽  
Yao Wang ◽  
Julie K. Pfeiffer
Keyword(s):  
Gastrointestinal Tract ◽  
Viral Replication ◽  
Sex Hormones ◽  
Viral Infections ◽  
Type I Interferon ◽  
Enteric Virus ◽  
Interferon Response ◽  
Sex Bias ◽  
Type I ◽  
Peripheral Tissues

ABSTRACT Coxsackievirus is an enteric virus that initiates infection in the gastrointestinal tract before disseminating to peripheral tissues to cause disease, but intestinal factors that influence viral replication are understudied. Furthermore, a sex bias for severe sequelae from coxsackievirus infections has been observed in humans. While mouse models mimicking human pathogenesis have been well characterized, many of these experiments use intraperitoneal injection of coxsackievirus to infect mice, bypassing the intestine. In light of recent studies identifying intestinal factors, such as the microbiota, that alter enteric viral replication, we sought to investigate coxsackievirus replication within the intestine. Here, we orally infected mice with coxsackievirus B3 (CVB3) and found that CVB3 replication in the intestine is sex dependent. CVB3 replicated efficiently in the intestine of male mice but not female mice. Additionally, we found that the type I interferon response and sex hormones can alter both viral replication and lethality. Overall, these data suggest that sex and the immune response play a vital role in CVB3 replication in the intestine and should be considered in light of the sex bias observed in human disease. IMPORTANCE Sex bias in severe sequelae from enteric viral infections has been observed. Since viruses have evolved to achieve optimal levels of fitness in their environmental niches, it is imperative to study viruses at the site of initial replication. Here, we used an oral inoculation system for CVB3, which follows the natural route of infection in the gastrointestinal tract. We found that sex can influence the replication of CVB3 in the intestine. Additionally, the type I interferon response and sex hormones alter both CVB3 intestinal replication and lethality. Overall this work highlights the fact that sex should be considered in investigations of enteric viral replication and pathogenesis.

scholarly journals Interrelationships of Interferon and Immunity During Viral Infections

1970 ◽  
Vol 56 (1) ◽  
pp. 212-226 ◽  
Author(s):  
Lowell A. Glasgow
Keyword(s):  
Immune Responses ◽  
Vaccinia Virus ◽  
Host Resistance ◽  
Host Response ◽  
Viral Infections ◽  
Cell Interaction ◽  
Relative Importance ◽  
Host Interaction ◽  
Interferon Responses

Interferon is one determinant of host resistance. The immune responses, cellular or humoral, are other components. Cell-mediated responses appear to be involved in host resistance to certain viral infections, particularly the herpesvirus group and vaccinia virus. It is suggested that immune and interferon responses may complement one another and contribute to host resistance. The relative importance of each component depends upon the virus-host interaction. Finally, evidence has been presented which suggests that production of interferon as a result of antigen-sensitized cell interaction may further link these two components of the host response.

scholarly journals A 29-mRNA host response test from blood accurately distinguishes bacterial and viral infections among emergency department patients

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Asimina Safarika ◽  
James W. Wacker ◽  
Konstantinos Katsaros ◽  
Nicky Solomonidi ◽  
George Giannikopoulos ◽  
...  
Keyword(s):  
Emergency Department ◽  
Host Response ◽  
Viral Infections ◽  
Acute Infection ◽  
Chronic Obstructive ◽  
Infection Status ◽  
Suspected Sepsis ◽  
Response Test ◽  
Cell Counts ◽  
Rule Out

Abstract Background Whether or not to administer antibiotics is a common and challenging clinical decision in patients with suspected infections presenting to the emergency department (ED). We prospectively validate InSep, a 29-mRNA blood-based host response test for the prediction of bacterial and viral infections. Methods The PROMPT trial is a prospective, non-interventional, multi-center clinical study that enrolled 397 adult patients presenting to the ED with signs of acute infection and at least one vital sign change. The infection status was adjudicated using chart review (including a syndromic molecular respiratory panel, procalcitonin and C-reactive protein) by three infectious disease physicians blinded to InSep results. InSep (version BVN-2) was performed using PAXgene Blood RNA processed and quantified on NanoString nCounter SPRINT. InSep results (likelihood of bacterial and viral infection) were compared to the adjudicated infection status. Results Subject mean age was 64 years, comorbidities were significant for diabetes (17.1%), chronic obstructive pulmonary disease (13.6%), and severe neurological disease (6.8%); 16.9% of subjects were immunocompromised. Infections were adjudicated as bacterial (14.1%), viral (11.3%) and noninfected (0.25%): 74.1% of subjects were adjudicated as indeterminate. InSep distinguished bacterial vs. viral/noninfected patients and viral vs. bacterial/noninfected patients using consensus adjudication with AUROCs of 0.94 (95% CI 0.90–0.99) and 0.90 (95% CI 0.83–0.96), respectively. AUROCs for bacterial vs. viral/noninfected patients were 0.88 (95% CI 0.79–0.96) for PCT, 0.80 (95% CI 0.72–89) for CRP and 0.78 (95% CI 0.69–0.87) for white blood cell counts (of note, the latter biomarkers were provided as part of clinical adjudication). To enable clinical actionability, InSep incorporates score cutoffs to allocate patients into interpretation bands. The Very Likely (rule in) InSep bacterial band showed a specificity of 98% compared to 94% for the corresponding PCT band (> 0.5 µg/L); the Very Unlikely (rule-out) band showed a sensitivity of 95% for InSep compared to 86% for PCT. For the detection of viral infections, InSep demonstrated a specificity of 93% for the Very Likely band (rule in) and a sensitivity of 96% for the Very Unlikely band (rule out). Conclusions InSep demonstrated high accuracy for predicting the presence of both bacterial and viral infections in ED patients with suspected acute infections or suspected sepsis. When translated into a rapid, point-of-care test, InSep will provide ED physicians with actionable results supporting early informed treatment decisions to improve patient outcomes while upholding antimicrobial stewardship. Registration number at Clinicaltrials.gov NCT 03295825.

scholarly journals Endogenous mitochondrial double‐stranded RNA is not an activator of the type I interferon response in human pancreatic beta cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexandra Coomans de Brachène ◽  
Angela Castela ◽  
Anyïshai E. Musuaya ◽  
Lorella Marselli ◽  
Piero Marchetti ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Viral Infections ◽  
Human Islets ◽  
Interferon Response ◽  
Interferon Α ◽  
Type I ◽  
Type I Ifn ◽  
Danger Signal ◽  
Double Stranded Rna

Abstract Background Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive destruction of pancreatic beta cells. Interferon-α (IFNα), an antiviral cytokine, is expressed in the pancreatic islets in early T1D, which may be secondary to viral infections. However, not all patients harboring a type I IFN signature present signals of viral infection, suggesting that this response might be initiated by other “danger signals”. Accumulation of mitochondrial double-stranded RNA (mtdsRNA; a danger signal), secondary to silencing of members of the mitochondrial degradosome, PNPT1 and SUV3, has been described to activate the innate immune response. Methods To evaluate whether mtdsRNA represents a “danger signal” for pancreatic beta cells in the context of T1D, we silenced PNPT1 and/or SUV3 in slowly proliferating human insulin-secreting EndoC-βH1 cells and in non-proliferating primary human beta cells and evaluated dsRNA accumulation by immunofluorescence and the type I IFN response by western blotting and RT-qPCR. Results Only the simultaneous silencing of PNPT1/SUV3 induced dsRNA accumulation in EndoC-βH1 cells but not in dispersed human islets, and there was no induction of a type I IFN response. By contrast, silencing of these two genes individually was enough to induce dsRNA accumulation in fibroblasts present in the human islet preparations. Conclusions These data suggest that accumulation of endogenous mtdsRNA following degradosome knockdown depends on the proliferative capacity of the cells and is not a mediator of the type I IFN response in human pancreatic beta cells.

scholarly journals Differential levels of IFNα subtypes in autoimmunity and viral infection

2021 ◽  
Author(s):  
Vincent Bondet ◽  
Mathieu P Rodero ◽  
Celine Posseme ◽  
Pierre Bost ◽  
Jeremie Decalf ◽  
...  
Keyword(s):  
Viral Infection ◽  
Host Response ◽  
Viral Infections ◽  
High Sensitivity ◽  
Type I Interferons ◽  
Type I ◽  
Effector Functions ◽  
Unusual Phenotype ◽  
Digital Elisa ◽  
Cellular Stimulation

Type I interferons are essential for host response to viral infections, while dysregulation of their response can result in autoinflammation or autoimmunity. Among IFNα (alpha) responses, 13 subtypes exist that signal through the same receptor, but have been reported to have different effector functions. However, the lack of available tools for discriminating these closely related subtypes, in particular at the protein level, has restricted the study of their differential roles in disease. We developed a digital ELISA with specificity and high sensitivity for the IFNα2 subtype. Application of this assay, in parallel with our previously described pan-IFNα assay, allowed us to study different IFNα protein responses following cellular stimulation and in diverse patient cohorts. We observed different ratios of IFNα protein responses between viral infection and autoimmune patients. This analysis also revealed a small percentage of autoimmune patients with high IFNα2 protein measurements but low pan-IFNα measurements. Correlation with an ISG score and functional activity showed that in this small sub group of patients, IFNα2 protein measurements did not reflect its biological activity. This unusual phenotype was partly explained by the presence of anti-IFNα auto-antibodies in a subset of autoimmune patients. This study reports ultrasensitive assays for the study of IFNα proteins in patient samples and highlights the insights that can be obtained from the use of multiple phenotypic readouts in translational and clinical studies.

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