scholarly journals COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases

2021 ◽  
Vol 22 (14) ◽  
pp. 7481
Author(s):  
Pier-Angelo Tovo ◽  
Silvia Garazzino ◽  
Valentina Daprà ◽  
Giulia Pruccoli ◽  
Cristina Calvi ◽  
...  
Keyword(s):  
Viral Infections ◽  
Severe Disease ◽  
Endogenous Retroviruses ◽  
Type I ◽  
Human Endogenous Retroviruses ◽  
Moderate Disease ◽  
Amplification Assay ◽  
Positive Correlations ◽  
Inducible Genes ◽  
Inflammatory Syndrome

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. RIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children nd in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19-infected children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.

scholarly journals CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity

Infection ◽  
2021 ◽  
Author(s):  
Jan-Moritz Doehn ◽  
Christoph Tabeling ◽  
Robert Biesen ◽  
Jacopo Saccomanno ◽  
Elena Madlung ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Disease Severity ◽  
Clinical Studies ◽  
Viral Infections ◽  
Severe Disease ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Signaling ◽  
Expression Levels

AbstractCoronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.

scholarly journals The Relationship of the Mechanisms of the Pathogenesis of Multiple Sclerosis and the Expression of Endogenous Retroviruses

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 464
Author(s):  
Vera R. Lezhnyova ◽  
Ekaterina V. Martynova ◽  
Timur I. Khaiboullin ◽  
Richard A. Urbanowicz ◽  
Svetlana F. Khaiboullina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Viral Infections ◽  
Endogenous Retroviruses ◽  
Epigenetic Mechanisms ◽  
Humoral Factors ◽  
Human Endogenous Retroviruses ◽  
Relationship Of ◽  
The Relationship

Two human endogenous retroviruses of the HERV-W family can act as cofactors triggering multiple sclerosis (MS): MS-associated retrovirus (MSRV) and ERVWE1. Endogenous retroviral elements are believed to have integrated in our ancestors’ DNA millions of years ago. Their involvement in the pathogenesis of various diseases, including neurodegenerative pathologies, has been demonstrated. Numerous studies have shown a correlation between the deterioration of patients’ health and increased expression of endogenous retroviruses. The exact causes and mechanisms of endogenous retroviruses activation remains unknown, which hampers development of therapeutics. In this review, we will summarize the main characteristics of human endogenous W retroviruses and describe the putative mechanisms of activation, including epigenetic mechanisms, humoral factors as well as the role of the exogenous viral infections.

scholarly journals Possible harm from glucocorticoid drugs misuse in the early phase of SARS-CoV-2 infection: a narrative review of the evidence

2021 ◽  
Author(s):  
Riccardo Sarzani ◽  
Francesco Spannella ◽  
Federico Giulietti ◽  
Chiara Di Pentima ◽  
Piero Giordano ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infections ◽  
Severe Disease ◽  
Positive Outcome ◽  
Supplemental Oxygen ◽  
Time Interval ◽  
Type I ◽  
Life Threatening ◽  
The Right ◽  
Supplemental Oxygen Therapy

AbstractSince the publication of the RECOVERY trial, the use of glucocorticoid drugs (GC) has spread for the treatment of severe COVID-19 worldwide. However, the benefit of dexamethasone was largest in patients who received mechanical ventilation or supplemental oxygen therapy, while no benefit was found among patients without hypoxemia. In addition, a positive outcome was found in patients who received dexamethasone after several days of symptoms, while possible harm could exist if administered early. The right time interval for GC administration is still a matter of debate. Previous studies showed that an early GC use during the first phase of the disease, when viral replication peaks, may negatively affect the innate immune response through several mechanisms, such as the inhibition of pro-inflammatory and antiviral cytokine production and signaling pathway, including type I interferon, that is fundamental to counteract the virus and that was found to be impaired in several patients with life-threatening COVID-19. The GC misuse can lead to a more severe disease even in patients who do not have the established risk factors, such as obesity and cardiovascular diseases. In our focused review, we describe the role of immune response in viral infections, especially SARS-CoV-2, and discuss the potential harms of GC misuse in COVID-19.

scholarly journals Serum β2-microglobulin levels in Coronavirus disease 2019 (Covid-19): Another prognosticator of disease severity?

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247758
Author(s):  
Walter Conca ◽  
Mayyadah Alabdely ◽  
Faisal Albaiz ◽  
Michael Warren Foster ◽  
Maha Alamri ◽  
...  
Keyword(s):  
Disease Severity ◽  
Viral Infections ◽  
Linear Trend ◽  
Severe Disease ◽  
Tertiary Care ◽  
Care Hospital ◽  
Mhc I ◽  
Mild Disease ◽  
Moderate Disease ◽  
Single Center Study

β2-microglobulin (β2-m), a 11.8 kDa protein, pairs non-covalently with the α3 domain of the major histocompatibility class (MHC) I α-chain and is essential for the conformation of the MHC class I protein complex. Shed β2-m is measurable in circulation, and various disorders are accompanied by increases in β2-m levels, including several viral infections. Therefore, we explored whether β2-m levels could also be elevated in Coronavirus disease 2019 (Covid-19) and whether they predict disease severity. Serum β2-m levels were measured in a cohort of 34 patients infected with SARS-CoV-2 on admission to a tertiary care hospital in Riyadh, Saudi Arabia, as well as in an approximately age-sex matched group of 34 uninfected controls. Mean β2-m level was 3.25±1.68 mg/l (reference range 0.8–2.2 mg/l) in patients (mean age 48.2±21.6) and 1.98±0.61 mg/l in controls (mean age 48.2±21.6). 17 patients (mean age 36.9± 18.0) with mean β2-m levels of 2.27±0.64 mg/l had mild disease by WHO severity categorization, 12 patients (mean age 53.3±18.1) with mean β2-m levels of 3.57±1.39 mg/l had moderate disease, and five patients (of whom 2 died; mean age 74.4±13.8) with mean β2-m levels of 5.85±1.85 mg/l had severe disease (P < = 0.001, by ANOVA test for linear trend). In multivariate ordinal regression β2-m levels were the only significant predictor of disease severity. Our findings suggest that higher β2-m levels could be an early indicator of severity of disease and predict outcome of Covid-19. As the main limitations of the study are a single-center study, sample size and ethnicity, these results need confirmation in larger cohorts outside the Arabian Peninsula in order to delineate the value of β2-m measurements. The role of β2-m in the etiology and pathogenesis of severe Covid-19 remains to be elucidated.

scholarly journals Divergent COVID-19 Disease Trajectories Predicted by a DAMP-Centered Immune Network Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Judy D. Day ◽  
Soojin Park ◽  
Benjamin L. Ranard ◽  
Harinder Singh ◽  
Carson C. Chow ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Load ◽  
Neutralizing Antibodies ◽  
Viral Infections ◽  
Temporal Dynamics ◽  
Severe Disease ◽  
Type I ◽  
Modeling Framework ◽  
Molecular Pattern ◽  
Immune Network Model

COVID-19 presentations range from mild to moderate through severe disease but also manifest with persistent illness or viral recrudescence. We hypothesized that the spectrum of COVID-19 disease manifestations was a consequence of SARS-CoV-2-mediated delay in the pathogen-associated molecular pattern (PAMP) response, including dampened type I interferon signaling, thereby shifting the balance of the immune response to be dominated by damage-associated molecular pattern (DAMP) signaling. To test the hypothesis, we constructed a parsimonious mechanistic mathematical model. After calibration of the model for initial viral load and then by varying a few key parameters, we show that the core model generates four distinct viral load, immune response and associated disease trajectories termed “patient archetypes”, whose temporal dynamics are reflected in clinical data from hospitalized COVID-19 patients. The model also accounts for responses to corticosteroid therapy and predicts that vaccine-induced neutralizing antibodies and cellular memory will be protective, including from severe COVID-19 disease. This generalizable modeling framework could be used to analyze protective and pathogenic immune responses to diverse viral infections.

scholarly journals Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Glauco Akelinghton Freire Vitiello ◽  
Wallax Augusto Silva Ferreira ◽  
Vladmir Cláudio Cordeiro de Lima ◽  
Tiago da Silva Medina
Keyword(s):  
Steady State ◽  
Viral Infections ◽  
Immune Cell ◽  
Predictive Marker ◽  
Innate Immune ◽  
Endogenous Retroviruses ◽  
Type I ◽  
Show Evidence ◽  
Interferon Pathway ◽  
Immunotherapy Target

In recent years, it became apparent that cancers either associated with viral infections or aberrantly expressing endogenous retroviral elements (EREs) are more immunogenic, exhibiting an intense intra-tumor immune cell infiltration characterized by a robust cytolytic apparatus. On the other hand, epigenetic regulation of EREs is crucial to maintain steady-state conditions and cell homeostasis. In line with this, epigenetic disruptions within steady-state cells can lead to cancer development and trigger the release of EREs into the cytoplasmic compartment. As such, detection of viral molecules by intracellular innate immune sensors leads to the production of type I and type III interferons that act to induce an antiviral state, thus restraining viral replication. This knowledge has recently gained momentum due to the possibility of triggering intratumoral activation of interferon responses, which could be used as an adjuvant to elicit strong anti-tumor immune responses that ultimately lead to a cascade of cytokine production. Accordingly, several therapeutic approaches are currently being tested using this rationale to improve responses to cancer immunotherapies. In this review, we discuss the immune mechanisms operating in viral infections, show evidence that exogenous viruses and endogenous retroviruses in cancer may enhance tumor immunogenicity, dissect the epigenetic control of EREs, and point to interferon pathway activation in the tumor milieu as a promising molecular predictive marker and immunotherapy target. Finally, we briefly discuss current strategies to modulate these responses within tumor tissues, including the clinical use of innate immune receptor agonists and DNA demethylating agents.

scholarly journals Human Endogenous Retroviruses and Type 1 Diabetes

2019 ◽  
Vol 19 (12) ◽  
Author(s):  
Sandrine Levet ◽  
B. Charvet ◽  
A. Bertin ◽  
A. Deschaumes ◽  
H. Perron ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Environmental Factors ◽  
Genetic Susceptibility ◽  
Envelope Protein ◽  
Pancreatic Beta Cells ◽  
Viral Infections ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Direct Toxicity

Abstract Purpose of the Review The aim of this review is to discuss recent data pointing at an involvement of human endogenous retroviruses (HERVs) in type 1 diabetes (T1D) onset and progression. Recent Findings The envelope protein of HERV-W family, named HERV-W-Env, was detected in pancreata from T1D patients and was shown to display pro-inflammatory properties and direct toxicity toward pancreatic beta cells. Summary The etiopathogenesis of T1D remains elusive, even if conventional environmental viral infections have been recurrently involved. Nonetheless, a new category of pathogens may provide the missing link between genetic susceptibility and environmental factors long thought to contribute to T1D onset. A number of studies have now shown that HERV sequences, which are normally inactivated or repressed in the human genome, could be activated by environmental viruses. Thus, if similarly activated by viruses associated with T1D, disregarded HERV genes may underlie T1D genetic susceptibility. Moreover, once expressed, HERV elements may display broad pathogenic properties, which identify them as potential new therapeutic targets.

scholarly journals Activation of cGAS/STING pathway upon paramyxovirus infection

2020 ◽  
Author(s):  
Mathieu Iampietro ◽  
Claire Dumont ◽  
Cyrille Mathieu ◽  
Julia Spanier ◽  
Jonathan Robert ◽  
...  
Keyword(s):  
Measles Virus ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Severe Disease ◽  
Nipah Virus ◽  
Innate Immune ◽  
Type I ◽  
Interferon Production ◽  
Host Protection ◽  
Sting Pathway

SUMMARYDuring inflammatory diseases, cancer and infection, the cGAS/STING pathway is known to recognize foreign or self-DNA in the cytosol and activate an innate immune response. Here, we report that negative-strand RNA paramyxoviruses, Nipah virus (NiV) and Measles virus (MeV), can also trigger the cGAS/STING axis. While mice deficient for MyD88, TRIF and MAVS still moderately control NiV infection when compared to WT mice, additional STING deficiency resulted in 100% lethality, suggesting synergistic roles of these pathways in host protection. Moreover, deletion of cGAS or STING resulted in decreased type-I interferon production with enhanced paramyxoviral infection in both human and murine cells. Finally, the phosphorylation and ubiquitination of STING, observed during viral infections, confirmed the activation of cGAS/STING pathway by NiV and MeV. Our data suggest that cGAS/STING activation is critical in controlling paramyxovirus infection, and possibly represent attractive targets to develop countermeasures against severe disease induced by these pathogens.

scholarly journals Chronic HCV Infection Is Associated with Overexpression of Human Endogenous Retroviruses that Persists after Drug-Induced Viral Clearance

2020 ◽  
Vol 21 (11) ◽  
pp. 3980
Author(s):  
Pier-Angelo Tovo ◽  
Silvia Garazzino ◽  
Valentina Daprà ◽  
Carla Alliaudi ◽  
Erika Silvestro ◽  
...  
Keyword(s):  
Viral Infections ◽  
White Blood Cells ◽  
Autoimmune Disorders ◽  
Viral Clearance ◽  
Hcv Infection ◽  
Endogenous Retroviruses ◽  
Drug Induced ◽  
Human Endogenous Retroviruses ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Chronic hepatitis C virus (HCV) infection is associated with several hepatic and extrahepatic complications, including cancers and autoimmune disorders, whose frequency is reduced but not abolished after drug-induced viral clearance. The causes of these complications and of their persistence are ill-defined. Human endogenous retroviruses (HERVs) are remnants of ancestral infections and constitute 8% of the human genome. Most HERV elements are inactive, but some are transcribed. HERV overexpression is associated with many cancers and autoimmune diseases with a putative pathogenetic role. Several viral infections trigger HERV activation, but there are no studies on HCV-infected subjects. We assessed, through a PCR real-time amplification assay, the transcription levels of the pol genes of HERV-H, -K, and -W, and of their repressor TRIM28 in white blood cells (WBCs) of vertically infected children, both before and after therapy with direct-acting antivirals (DAAs). The results documented significantly higher expressions of HERV-H-pol and HERV-K-pol, not of HERV-W-pol, in HCV-infected subjects as compared to age-matched controls. HERV RNA levels remained unchanged after DAA-driven viral clearance. No significant variations in transcription levels of TRIM28 were observed in infected subjects. Our findings demonstrate HERV-H-pol and HERV-K-pol overexpression in subjects with chronic HCV infection, without variations after a positive response to DAAs; this might justify their predisposition to cancers and autoimmune disorders that persist after a DAA-induced resolution of viremia.

scholarly journals Value of blood IFN-I levels in COVID-19 management

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Burak Arslan ◽  
Aylin Sepici Dinçel
Keyword(s):  
Viral Infection ◽  
Limit Of Detection ◽  
Severe Disease ◽  
Serum Levels ◽  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
System Disease ◽  
Moderate Disease ◽  
Respiratory System Disease

AbstractCoronavirus disease 2019 (COVID-19) which is a respiratory system disease has created inevitable pandemic. In the course of disease; the uncontrolled inflammatory response may cause tissue damage. 80–90% of patients undergo mild-to-moderate disease symptoms, the rest of the patients proceeds to critical or severe disease. Type I Interferons (IFN–I) are crucial immune mediators in order to host responses to viral infection likewise those are major components of the innate immune system moreover serve as critical antiviral molecules. IFN-I are within the first cytokines secreted during a viral infection. Until now, IFN-I response has been evaluated in patients with COVID-19 in a few publications and its contribution to the viral load control and inflammation is very little known. In those studies, the researchers have found that IFN-I deficiency which characterized by no IFN- β and low IFN- α production and activity is a hallmark of severe and critical COVID-19. Until recently, measurement of circulating serum levels of IFN-α have been limited owing to the limits of conventional immunoassay technology. Limit of detection problems of immunoassays has started to figure out thanks to SIMOA. On the top of that, generally the platforms that use SIMOA technology is 10–100 fold more sensitive than most conventional immunoassays. We should strive to do research that includes IFN-I with using platforms that include SIMOA technology, especially in severe COVID-19.

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