interferon pathway
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2022 ◽  
Vol 12 ◽  
Author(s):  
Qian Zhang ◽  
Dan Yi ◽  
Changzheng Ji ◽  
Tao Wu ◽  
Manli Wang ◽  
...  

Porcine epidemic diarrhea virus (PEDV) has reemerged as the main pathogen of piglets due to its high mutation feature. Monolaurin (ML) is a natural compound with a wide range of antibacterial and antiviral activities. However, the role of ML in PEDV infection is still unknown. This study aimed to evaluate the effect of ML on the growth performance, intestinal function, virus replication and cytokine response in piglets infected with PEDV, and to reveal the mechanism through proteomics analysis. Piglets were orally administrated with ML at a dose of 100 mg/kg·BW for 7 days before PEDV infection. Results showed that although there was no significant effect on the growth performance of piglets, ML administration alleviated the diarrhea caused by PEDV infection. ML administration promoted the recovery of intestinal villi, thereby improving intestinal function. Meanwhile, PEDV replication was significantly inhibited, and PEDV-induced expression of IL-6 and IL-8 were decreased with ML administration. Proteomics analyses showed that 38 proteins were differentially expressed between PEDV and ML+PEDV groups and were significantly enriched in the interferon-related pathways. This suggests ML could promote the restoration of homeostasis by regulating the interferon pathway. Overall, the present study demonstrated ML could confer a protective effect against PEDV infection in piglets and may be developed as a drug or feed additive to prevent and control PEDV disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Youwei Zhu ◽  
Zhaoyang Zhang ◽  
Jia Song ◽  
Weizhou Qian ◽  
Xiangqian Gu ◽  
...  

Infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the rapid spread of coronavirus disease 2019 (COVID-19), has generated a public health crisis worldwide. The molecular mechanisms of SARS-CoV-2 infection and virus–host interactions are still unclear. In this study, we identified four unique microRNA-like small RNAs encoded by SARS-CoV-2. SCV2-miR-ORF1ab-1-3p and SCV2-miR-ORF1ab-2-5p play an important role in evasion of type I interferon response through targeting several genes in type I interferon signaling pathway. Particularly worth mentioning is that highly expressed SCV2-miR-ORF1ab-2-5p inhibits some key genes in the host innate immune response, such as IRF7, IRF9, STAT2, OAS1, and OAS2. SCV2-miR-ORF1ab-2-5p has also been found to mediate allelic differential expression of COVID-19-susceptible gene OAS1. In conclusion, these results suggest that SARS-CoV-2 uses its miRNAs to evade the type I interferon response and links the functional viral sequence to the susceptible genetic background of the host.


2021 ◽  
Author(s):  
Touraj Khosravi‐Hafshejani ◽  
Mehran Ghoreishi ◽  
Cristian Vera Kellet ◽  
Richard I. Crawford ◽  
Magdalena Martinka ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Glauco Akelinghton Freire Vitiello ◽  
Wallax Augusto Silva Ferreira ◽  
Vladmir Cláudio Cordeiro de Lima ◽  
Tiago da Silva Medina

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.


2021 ◽  
Author(s):  
Kati Tormanen ◽  
Shaohui Wang ◽  
Harry H. Matundan ◽  
Jack Yu ◽  
Ujjaldeep Jaggi ◽  
...  

HSV-1 latency associated transcript (LAT) plays a significant role in efficient establishment of latency and reactivation. LAT has antiapoptotic activity and downregulates expression of components of the Type I interferon pathway. LAT also specifically activates expression of the herpesvirus entry mediator (HVEM), one of seven known receptors used by HSV-1 for cell entry that is crucial for latency and reactivation. However, the mechanism by which LAT regulates HVEM expression is not known. LAT encodes two sncRNAs that are not miRNAs, within its 1.5 kb stable transcript, which also have antiapoptotic activity. These sncRNAs may encode short peptides, but experimental evidence is lacking. Here, we demonstrate that these two sncRNAs control HVEM expression by activating its promoter. Both sncRNAs are required for WT level of activation of HVEM and sncRNA1 is more important in HVEM activation than sncRNA2. Disruption of a putative start codon in sncRNA1 and sncRNA2 sequences reduced HVEM promoter activity, suggesting that sncRNAs may encode a protein. However, we did not detect peptide binding using two chromatin immunoprecipitation (ChIP) approaches and a web-based algorithm predicts low probability that the putative peptides bind to DNA. In addition, computational modeling predicts that sncRNA molecules bind with high affinity to the HVEM promoter and deletion of these binding sites to sncRNA1, sncRNA2 or both reduced HVEM promoter activity. Together, our data suggests that sncRNAs exert their function as RNA molecules, not as proteins, and we provide a model for the predicted binding affinities and binding sites of sncRNA1 and sncRNA2 in the HVEM promoter. IMPORTANCE HSV-1 causes recurrent ocular infections, which is the leading cause of corneal scarring and blindness. Corneal scarring is caused by the host immune response to repeated reactivation events. LAT functions by regulating latency and reactivation, in part by inhibiting apoptosis and activating HVEM expression. However, the mechanism used by LAT to control of HVEM expression is unclear. Here, we demonstrate that two sncRNAs encoded within the 1.5 kb LAT transcript activate HVEM expression by binding to two regions of its promoter. Interfering with these interactions may reduce latency and thereby eye disease associated with reactivation.


2021 ◽  
Vol 22 (20) ◽  
pp. 11286
Author(s):  
Madhu Ramaswamy ◽  
Raj Tummala ◽  
Katie Streicher ◽  
Andre Nogueira da Costa ◽  
Philip. Z. Brohawn

Therapeutic success in treating patients with systemic lupus erythematosus (SLE) is limited by the multivariate disease etiology, multi-organ presentation, systemic involvement, and complex immunopathogenesis. Agents targeting B-cell differentiation and survival are not efficacious for all patients, indicating a need to target other inflammatory mediators. One such target is the type I interferon pathway. Type I interferons upregulate interferon gene signatures and mediate critical antiviral responses. Dysregulated type I interferon signaling is detectable in many patients with SLE and other autoimmune diseases, and the extent of this dysregulation is associated with disease severity, making type I interferons therapeutically tangible targets. The recent approval of the type I interferon-blocking antibody, anifrolumab, by the US Food and Drug Administration for the treatment of patients with SLE demonstrates the value of targeting this pathway. Nevertheless, the interferon pathway has pleiotropic biology, with multiple cellular targets and signaling components that are incompletely understood. Deconvoluting the complexity of the type I interferon pathway and its intersection with lupus disease pathology will be valuable for further development of targeted SLE therapeutics. This review summarizes the immune mediators of the interferon pathway, its association with disease pathogenesis, and therapeutic modalities targeting the dysregulated interferon pathway.


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257418
Author(s):  
Carolina dos Santos Amaral ◽  
Gabrielle Rebeca Everling Correa ◽  
Lady Katerine Serrano Mujica ◽  
Mariani Farias Fiorenza ◽  
Suzan Gonçalves Rosa ◽  
...  

One of the major causes of early pregnancy loss is heat stress. In ruminants, interferon tau (IFNT) is the embryo signal to the mother. Once the interferon signaling pathway is activated, it drives gene expression for interferon-stimulated genes (ISGs) and alters neutrophils responses. The aim of the present study was to evaluate interferon (IFN) pathway, ISGs and gene expression in polymorphonuclear leukocytes (PMN) and oxidative stress in dairy cows under heat stress. Pregnant cows had their estrous cycle synchronized and randomly assigned to a comfort or heat stress group. Blood samples were collected at artificial insemination (AI) and on Days 10, 14 and 18 following AI. Pregnant cows were pregnancy checked by ultrasound on Day 30 and confirmed on Day 60 post-AI. Results are presented as mean ± SEM. The corpus luteum (CL) diameter was not different between groups of pregnant cows; concentration of progesterone of pregnant cows on Day 18 following AI was greater in comfort group compared to heat stressed group. Comfort pregnant cows had higher expression of all analyzed genes from interferon pathway, except for IFNAR1, on both Days 14 and 18. Conversely, heat stressed cows did not show altered expression of IFNT pathway genes and ISGs between Days 10, 14, and 18 after AI. The oxidative stress, determined as malondialdehyde (MDA) levels, was greater in heat stress group on Days 10, 14 and 18, independent of pregnancy status. Heat stress negatively influences expression of ISGs, IFN pathway gene expression in neutrophils, and oxidative stress. Our data suggest that lower conception rates in cows under heat stress are multifactorial, with the association of interferon pathway activation and the unbalanced oxidative stress being main contributing factors.


2021 ◽  
Vol 12 ◽  
Author(s):  
Leonid Gozman ◽  
Kellie Perry ◽  
Dimitri Nikogosov ◽  
Ilya Klabukov ◽  
Artem Shevlyakov ◽  
...  

The rapid rise and global consequences of the novel coronavirus disease 19 (COVID-19) have again brought the focus of the scientific community on the possible host factors involved in patient response and outcome to exposure to the virus. The disease severity remains highly unpredictable, and individuals with none of the aforementioned risk factors may still develop severe COVID-19. It was shown that genotype-related factors like an ABO Blood Group affect COVID-19 severity, and the risk of infection with SARS-CoV-2 was higher for patients with blood type A and lower for patients with blood type O. Currently it is not clear which specific genes are associated with COVID-19 severity. The comparative analysis of COVID-19 and other viral infections allows us to predict that the variants within the interferon pathway genes may serve as markers of the magnitude of immune response to specific pathogens. In particular, various members of Class III interferons (lambda) are reviewed in detail.


2021 ◽  
Vol 8 (6) ◽  
pp. e1070
Author(s):  
Chao Zhang ◽  
Tian-Xiang Zhang ◽  
Ye Liu ◽  
Dongmei Jia ◽  
Pei Zeng ◽  
...  

Background and ObjectivesTo assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD).MethodsWe performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow in patients with NMOSD.ResultsAcross the tissue types tested, 4 major subpopulations of B cells with distinct signatures were identified: naive B cells, memory B cells, age-associated B cells, and antibody-secreting cells (ASCs). NMOSD B cells show proinflammatory activity and increased expression of chemokine receptor genes (CXCR3 and CXCR4). Circulating B cells display an increase of antigen presentation markers (CD40 and CD83), as well as activation signatures (FOS, CD69, and JUN). In contrast, the bone marrow B-cell population contains a large ASC fraction with increased oxidative and metabolic activity reflected by COX genes and ATP synthase genes. Typically, NMOSD B cells become hyperresponsive to type I interferon, which facilitates B-cell maturation and anti–aquaporin-4 autoantibody production. The pool of ASCs in blood and CSF were significantly elevated in NMOSD. Both CD19− and CD19+ ASCs could be ablated by tocilizumab, but not rituximab treatment in NMOSD.DiscussionB cells are compartmentally fine tuned toward autoreactivity in NMOSD and become hyperreactive to type I interferon. Inhibition of type I interferon pathway may provide a new therapeutic avenue for NMOSD.


Author(s):  
Laila Abdullah S. Alanazi ◽  
Abdullah Mohammed A. AL Madshush ◽  
Omniyyah Mohammed S. Alatawi ◽  
Asmaa Hamed M. Albuhairy ◽  
Jomana Khalid M. Aljohani ◽  
...  

Idiopathic inflammatory myopathies (IIMs) includes an unusual group of acute, chronic, and subacute developed diseases of skeletal muscle characterized by moderate to severe muscle weakness and inflammation.Polymyositis is generally considered to be a prototypic T cell-mediated autoimmune myopathy, while DM was traditionally associated with a humoral-driven microangiopathy, though the putative autoantibodies and their targets have yet to be identified, and there is increasing evidence implicating the type I interferon pathway in the pathogenesis of the disease.  Women between the ages of 50 and 70 are the most typically affected. Proximal muscular weakness is the most common clinical symptom. Inflammatory arthritis, Raynaud's phenomenon, myocarditis, and interstitial lung disease are all examples of extramuscular involvement. In this review, we overview updates in diagnosis and managements of polymyositis.


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