Journal articles: 'Type I interferons'

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Harris, Bethany D., Srilalitha Kuruganti, Ashlesha Deshpande, Paul A. Goepfert, W. Winn Chatham, and Mark R. Walter. "Characterization of Type-I IFN subtype autoantibodies and activity in SLE serum and urine." Lupus 29, no. 9 (2020): 1095–105. http://dx.doi.org/10.1177/0961203320935976.

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Background/objective Type-I interferons contribute to pathogenesis in systemic lupus erythematosus, including nephritis. Interferons consist of a family of 16 proteins yet are often characterized in patients without knowledge of the specific interferon subtypes involved. Different interferons may function in the kidneys, and other organs, relative to what is often measured in patient blood. Moreover, antibodies to interferons may potentially modulate systemic or organ-specific interferon activity. The aim of this study was to characterize global interferon activity levels and identify autoantibodies to the 12 interferon α subtypes in patient serum and urine. Methods Interferon activity levels in serum and urine were measured using an interferon bioassay. Anti-interferon and anti-cytokine autoantibodies were measured by ELISA. Serum and urine samples were also characterized for their ability to neutralize the biological activity of exogenously added interferons. Results Serum interferon activity was increased in 62% of systemic lupus erythematosus patient samples, relative to healthy donor controls, whereas binding interferon α autoantibodies to at least one interferon α subtype were found in 68% of the samples evaluated. High Systemic Lupus Erythematosus Disease Activity Index scores were significantly ( p = 0.001) associated with patient samples containing interferon α autoantibodies to three or more interferon α subtypes in their serum. Interferon α autoantibodies that potently block interferon activity were rare (∼5% of samples), but collectively bound to all 12 interferon α subtypes. Urine interferon activity and interferon α autoantibody profiles did not correlate with their serum counterparts, suggesting immune responses in systemic lupus erythematosus kidneys can be distinct from those measured in serum. Analysis of autoantibodies to 15 additional cytokines in serum identified higher frequencies of granulocyte-macrophage colony-stimulating factor and interleukin 17A autoantibodies, suggesting these signaling pathways may potentially contribute, with interferons, to systemic lupus erythematosus pathogenesis. Conclusions The measurement of autoantibodies to multiple interferon subtypes in serum and urine may provide an alternative method for following interferon-mediated systemic lupus erythematosus disease activity. The results suggest autoantibodies might be used for patient monitoring and/or identifying additional cytokine signaling pathways that are functioning in different systemic lupus erythematosus patients.

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Sozaeva, L. S. "The new immunological methods for diagnostics of type 1 autoimmune polyendocrine syndrome." Problems of Endocrinology 61, no. 3 (2015): 43–46. http://dx.doi.org/10.14341/probl201561343-46.

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Type 1 autoimmune polyglandular syndrome (type 1APS) is a rare genetic disease resulting from mutations in the AIRE gene. Diagnostics of this pathology is based not only on the results of genetic studies but also on the measurement of the level of antibodies against type 1 interferons, such as interferon-ω and interferon-α2. The present review of the literature is focused on type 1 interferons, anti-interferon antibodies, and pathophysiological characteristics of the processes induced by these antibodies.

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Le-Thi-Phuong, Thao, Gaëtan Thirion, and Jean-Paul Coutelier. "Distinct gamma interferon-production pathways in mice infected with lactate dehydrogenase-elevating virus." Journal of General Virology 88, no. 11 (2007): 3063–66. http://dx.doi.org/10.1099/vir.0.83242-0.

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Two distinct pathways of gamma interferon (IFN-γ) production have been found in mice infected with lactate dehydrogenase-elevating virus. Both pathways involve natural killer cells. The first is mostly interleukin-12-independent and is not controlled by type I interferons. The second, which is suppressed by type I interferons, leads to increased levels of IFN-γ production and requires the secretion of interleukin-12. This regulation of IFN-γ production by type I interferons may help to control indirect pathogenesis induced by this cytokine.

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Crow, Mary K., Mikhail Olferiev, and Kyriakos A. Kirou. "Type I Interferons in Autoimmune Disease." Annual Review of Pathology: Mechanisms of Disease 14, no. 1 (2019): 369–93. http://dx.doi.org/10.1146/annurev-pathol-020117-043952.

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Type I interferons, which make up the first cytokine family to be described and are the essential mediators of antivirus host defense, have emerged as central elements in the immunopathology of systemic autoimmune diseases, with systemic lupus erythematosus as the prototype. Lessons from investigation of interferon regulation following virus infection can be applied to lupus, with the conclusion that sustained production of type I interferon shifts nearly all components of the immune system toward pathologic functions that result in tissue damage and disease. We review recent data, mainly from studies of patients with systemic lupus erythematosus, that provide new insights into the mechanisms of induction and the immunologic consequences of chronic activation of the type I interferon pathway. Current concepts implicate endogenous nucleic acids, driving both cytosolic sensors and endosomal Toll-like receptors, in interferon pathway activation and suggest targets for development of novel therapeutics that may restore the immune system to health.

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Joyce, Margaret M., Robert C. Burghardt, Rodney D. Geisert, et al. "Pig Conceptuses Secrete Estrogen and Interferons to Differentially Regulate Uterine STAT1 in a Temporal and Cell Type-Specific Manner." Endocrinology 148, no. 9 (2007): 4420–31. http://dx.doi.org/10.1210/en.2007-0505.

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Conceptus trophectoderm and uterine luminal epithelial cells interact via endocrine, paracrine, and autocrine modulators to mediate pregnancy recognition and implantation. Pig conceptuses not only release estrogens for pregnancy recognition but also secrete interferons during implantation. Because interferon-stimulated genes are increased by interferons secreted for pregnancy recognition in ruminants, we asked whether the interferon-stimulated gene, STAT1, is up-regulated in pig endometrium by conceptus estrogens and/or interferons. STAT1 expression in response to day of pregnancy, estrogen injection, and intrauterine infusion of conceptus secretory proteins in pigs indicated 1) estrogen increases STAT1 in luminal epithelial cells, 2) conceptus secretory proteins that contain interferons increase STAT1 in stroma, 3) STAT1 increases in close proximity to the conceptus, and 4) early estrogen results in conceptus death and no STAT1 in stroma. The interactions of estrogen and interferons to regulate cell-type-specific expression of STAT1 highlight the complex interplay between endometrium and conceptus for pregnancy recognition and implantation.

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Pisanelli, Giuseppe, Ugo Pagnini, Giuseppe Iovane, and Adolfo García-Sastre. "Type I and Type II Interferon Antagonism Strategies Used by Paramyxoviridae: Previous and New Discoveries, in Comparison." Viruses 14, no. 5 (2022): 1107. http://dx.doi.org/10.3390/v14051107.

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Paramyxoviridae is a viral family within the order of Mononegavirales; they are negative single-strand RNA viruses that can cause significant diseases in both humans and animals. In order to replicate, paramyxoviruses–as any other viruses–have to bypass an important protective mechanism developed by the host’s cells: the defensive line driven by interferon. Once the viruses are recognized, the cells start the production of type I and type III interferons, which leads to the activation of hundreds of genes, many of which encode proteins with the specific function to reduce viral replication. Type II interferon is produced by active immune cells through a different signaling pathway, and activates a diverse range of genes with the same objective to block viral replication. As a result of this selective pressure, viruses have evolved different strategies to avoid the defensive function of interferons. The strategies employed by the different viral species to fight the interferon system include a number of sophisticated mechanisms. Here we analyzed the current status of the various strategies used by paramyxoviruses to subvert type I, II, and III interferon responses.

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He, Buyuan, James T. Tran, and David Jesse Sanchez. "Manipulation of Type I Interferon Signaling by HIV and AIDS-Associated Viruses." Journal of Immunology Research 2019 (April 4, 2019): 1–10. http://dx.doi.org/10.1155/2019/8685312.

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Type I Interferons were first described for their profound antiviral abilities in cell culture and animal models, and later, they were translated into potent antiviral therapeutics. However, as additional studies into the function of Type I Interferons progressed, it was also seen that pathogenic viruses have coevolved to encode potent mechanisms allowing them to evade or suppress the impact of Type I Interferons on their replication. For chronic viral infections, such as HIV and many of the AIDS-associated viruses, including HTLV, HCV, KSHV, and EBV, the clinical efficacy of Type I Interferons is limited by these mechanisms. Here, we review some of the ways that HIV and AIDS-associated viruses thrive in Type I Interferon-rich environments via mechanisms that block the function of this important antiviral cytokine. Overall, a better understanding of these mechanisms creates avenues to better understand the innate immune response to these viruses as well as plan the development of antivirals that would allow the natural antiviral effect of Type I Interferons to manifest during these infections.

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Domeier, Phillip P., and Ziaur S. M. Rahman. "Regulation of B Cell Responses in SLE by Three Classes of Interferons." International Journal of Molecular Sciences 22, no. 19 (2021): 10464. http://dx.doi.org/10.3390/ijms221910464.

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There are three classes of interferons (type 1, 2, and 3) that can contribute to the development and maintenance of various autoimmune diseases, including systemic lupus erythematosus (SLE). Each class of interferons promotes the generation of autoreactive B cells and SLE-associated autoantibodies by distinct signaling mechanisms. SLE patients treated with various type 1 interferon-blocking biologics have diverse outcomes, suggesting that additional environmental and genetic factors may dictate how these cytokines contribute to the development of autoreactive B cells and SLE. Understanding how each class of interferons controls B cell responses in SLE is necessary for developing optimized B cell- and interferon-targeted therapeutics. In this review, we will discuss how each class of interferons differentially promotes the loss of peripheral B cell tolerance and leads to the development of autoreactive B cells, autoantibodies, and SLE.

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De Maeyer, Edward, and Jaqueline De Maeyer-Guignard. "Type I Interferons." International Reviews of Immunology 17, no. 1-4 (1998): 53–73. http://dx.doi.org/10.3109/08830189809084487.

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10

Doehn, Jan-Moritz, Christoph Tabeling, Robert Biesen, et al. "CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity." Infection 49, no. 4 (2021): 757–62. http://dx.doi.org/10.1007/s15010-021-01606-9.

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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.

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11

Rauch, Isabella, Felix Rosebrock, Eva Hainzl, et al. "Noncanonical Effects of IRF9 in Intestinal Inflammation: More than Type I and Type III Interferons." Molecular and Cellular Biology 35, no. 13 (2015): 2332–43. http://dx.doi.org/10.1128/mcb.01498-14.

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The interferon (IFN)-stimulated gene factor 3 (ISGF3) transcription factor with its Stat1, Stat2, and interferon regulatory factor 9 (IRF9) subunits is employed for transcriptional responses downstream of receptors for type I interferons (IFN-I) that include IFN-α and IFN-β and type III interferons (IFN-III), also called IFN-λ. Here, we show in a murine model of dextran sodium sulfate (DSS)-induced colitis that IRF9 deficiency protects animals, whereas the combined loss of IFN-I and IFN-III receptors worsens their condition. We explain the different phenotypes by demonstrating a function of IRF9 in a noncanonical transcriptional complex with Stat1, apart from IFN-I and IFN-III signaling. Together, Stat1 and IRF9 produce a proinflammatory activity that overrides the benefits of the IFN-III response on intestinal epithelial cells. Our results further suggest that the CXCL10 chemokine gene is an important mediator of this proinflammatory activity. We thus establish IFN-λ as a potentially anticolitogenic cytokine and propose an important role for IRF9 as a component of noncanonical Stat complexes in the development of colitis.

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Aschman, Tom, Sandra Schaffer, Stylianos Iason Biniaris Georgallis, Antigoni Triantafyllopoulou, Peter Staeheli, and Reinhard E. Voll. "Interferon Lambda Regulates Cellular and Humoral Immunity in Pristane-Induced Lupus." International Journal of Molecular Sciences 22, no. 21 (2021): 11747. http://dx.doi.org/10.3390/ijms222111747.

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A pivotal role of type I interferons in systemic lupus erythematosus (SLE) is widely accepted. Type III interferons (IFN-λ) however, the most recently discovered cytokines grouped within the interferon family, have not been extensively studied in lupus disease models yet. Growing evidence suggests a role for IFN-λ in regulating both innate and adaptive immune responses, and increased serum concentrations have been described in multiple autoimmune diseases including SLE. Using the pristane-induced lupus model, we found that mice with defective IFN-λ receptors (Ifnlr1−/−) showed increased survival rates, decreased lipogranuloma formation and reduced anti-dsDNA autoantibody titers in the early phase of autoimmunity development compared to pristane-treated wild-type mice. Moreover, Ifnlr1−/− mice treated with pristane had reduced numbers of inflammatory mononuclear phagocytes and cNK cells in their kidneys, resembling untreated control mice. Systemically, circulating B cells and monocytes (CD115+Ly6C+) were reduced in pristane-treated Ifnlr1−/− mice. The present study supports a significant role for type III interferons in the pathogenesis of pristane-induced murine autoimmunity as well as in systemic and renal inflammation. Although the absence of type III interferon receptors does not completely prevent the development of autoantibodies, type III interferon signaling accelerates the development of autoimmunity and promotes a pro-inflammatory environment in autoimmune-prone hosts.

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Yum, Seoyun, Minghao Li, Yan Fang та Zhijian J. Chen. "TBK1 recruitment to STING activates both IRF3 and NF-κB that mediate immune defense against tumors and viral infections". Proceedings of the National Academy of Sciences 118, № 14 (2021): e2100225118. http://dx.doi.org/10.1073/pnas.2100225118.

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The induction of type I interferons through the transcription factor interferon regulatory factor 3 (IRF3) is considered a major outcome of stimulator of interferon genes (STING) activation that drives immune responses against DNA viruses and tumors. However, STING activation can also trigger other downstream pathways such as nuclear factor κB (NF-κB) signaling and autophagy, and the roles of interferon (IFN)-independent functions of STING in infectious diseases or cancer are not well understood. Here, we generated a STING mouse strain with a mutation (S365A) that disrupts IRF3 binding and therefore type I interferon induction but not NF-κB activation or autophagy induction. We also generated STING mice with mutations that disrupt the recruitment of TANK-binding kinase 1 (TBK1), which is important for both IRF3 and NF-κB activation but not autophagy induction (L373A or ∆CTT, which lacks the C-terminal tail). The STING-S365A mutant mice, but not L373A or ∆CTT mice, were still resistant to herpes simplex virus 1 (HSV-1) infections and mounted an antitumor response after cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) treatment despite the absence of STING-induced interferons. These results demonstrate that STING can function independently of type I interferons and autophagy, and that TBK1 recruitment to STING is essential for antiviral and antitumor immunity.

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Ramaswamy, Madhu, Raj Tummala, Katie Streicher, Andre Nogueira da Costa, and Philip Z. Brohawn. "The Pathogenesis, Molecular Mechanisms, and Therapeutic Potential of the Interferon Pathway in Systemic Lupus Erythematosus and Other Autoimmune Diseases." International Journal of Molecular Sciences 22, no. 20 (2021): 11286. http://dx.doi.org/10.3390/ijms222011286.

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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.

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Durbin, Joan E. "Ignoring type 1 interferons." Blood 107, no. 3 (2006): 847–48. http://dx.doi.org/10.1182/blood-2005-11-4582.

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Zimring, James C., Stephen Goodbourn, and Margaret K. Offermann. "Human Herpesvirus 8 Encodes an Interferon Regulatory Factor (IRF) Homolog That Represses IRF-1-Mediated Transcription." Journal of Virology 72, no. 1 (1998): 701–7. http://dx.doi.org/10.1128/jvi.72.1.701-707.1998.

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ABSTRACT Human herpesvirus 8 (HHV-8) is the probable viral etiologic agent for Kaposi’s sarcoma. The HHV-8 genome encodes viral interferon regulatory factor (vIRF), a gene product that has homology to the IRF family of transcription factors. We demonstrate that vIRF inhibits responses to type I and type II interferons and blocks IRF-1-mediated transcription. vIRF does not compete with IRF-1 for binding to DNA or complex directly with IRF-1. The ability of vIRF to block IRF-1-mediated transcription is independent of the DNA binding domains of both vIRF and IRF-1. These data suggest that vIRF may contribute to viral pathogenesis and cellular transformation by interfering with interferon- and IRF-1-mediated gene expression through a novel mechanism.

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Billi, Allison C. "Interfering too soon: Type I interferons can dampen antiviral immunity." Science Translational Medicine 12, no. 560 (2020): eabe1706. http://dx.doi.org/10.1126/scitranslmed.abe1706.

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Chronopoulou, Sofia, and Ilias Tsochantaridis. "Interferon Lambda: The Next Frontier in Antiviral Therapy?" Pharmaceuticals 18, no. 6 (2025): 785. https://doi.org/10.3390/ph18060785.

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Type III interferons (IFN-λ) are the most recently identified members of the interferon family, distantly related to type I interferons and members of the interleukin-10 (IL-10). Unlike type I interferons, which have broadly distributed cellular receptors, IFN-λ signals through a heterodimeric receptor complex with primary expression on epithelial cells. This restricted receptor distribution makes IFN-λ a favorable candidate for therapeutic and antiviral applications with reduced side effects. In this review, we describe the molecular structure, signaling mechanisms, and the role of IFN-λ in the innate immunity of epithelial tissue, which are its primary sites of action. Moreover, this review will summarize and critically examine the antiviral potential of IFN-λ based on all published clinical trials conducted for the treatment of COVID-19, and hepatitis B, C and D virus. Furthermore, this review suggests IFN-λ as a promising therapeutic recombinant protein, with special emphasis on its potential for production using alternative expression and advanced drug delivery systems. To emphasize its potential as a therapeutic intervention, the design and engineering of recombinant IFN-λ will be presented, with a focus on its lower side-effect profile compared to Type I interferons.

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Lokshina, E. E., V. V. Malinovskaya, O. V. Zaytseva, and S. U. Snitko. "Virus-induced asthma: how to achieve good disease control?" Voprosy praktičeskoj pediatrii 15, no. 6 (2020): 52–66. http://dx.doi.org/10.20953/1817-7646-2020-6-52-66.

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This article discusses the role of various respiratory viruses in the development of bronchial asthma and in triggering its exacerbation. It covers the pathogenetic mechanisms underlying virus-induced bronchial asthma and the importance of interferons for disease control. We summarized the results of international and Russian studies analyzing the utility of type 1 interferons for children and adults with virus-induced asthma exacerbations. Combination drugs containing recombinant α2b interferon plus α-tocopheryl acetate plus ascorbic acid have demonstrated their efficacy in the prevention and treatment of virus-induced asthma exacerbations in routine clinical practice. Moreover, these drugs were safe and well tolerated by patients, which opens new prospects for patients with virus-induced asthma. Key words: virus-induced bronchial asthma, respiratory viruses, children, interferons, therapy, recombinant α2b-interferon + α-tocopheryl acetate + ascorbic acid

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Zedan, Ahmad, Ashley D. Winters, Wei Yu, et al. "Antiviral Functions of Type I and Type III Interferons in the Olfactory Epithelium." Biomolecules 13, no. 12 (2023): 1762. http://dx.doi.org/10.3390/biom13121762.

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The olfactory neuroepithelium (OE) is one of the few neuronal tissues where environmental pathogens can gain direct access. Despite this vulnerable arrangement, little is known about the protective mechanisms in the OE to prevent viral infection and its antiviral responses. We systematically investigated acute responses in the olfactory mucosa upon exposure to vesicular stomatitis virus (VSV) via RNA-seq. VSVs were nasally inoculated into C57BL/6 mice. Olfactory mucosae were dissected for gene expression analysis at different time points after viral inoculation. Interferon functions were determined by comparing the viral load in interferon receptor knockout (Ifnar1−/− and Ifnlr1−/−) with wildtype OE. Antiviral responses were observed as early as 24 h after viral exposure in the olfactory mucosa. The rapidly upregulated transcripts observed included specific type I as well as type III interferons (Ifn) and interferon-stimulated genes. Genetic analyses demonstrated that both type I and type III IFN signaling are required for the suppression of viral replication in the olfactory mucosa. Exogenous IFN application effectively blocks viral replication in the OE. These findings reveal that the OE possesses an innate ability to suppress viral infection. Type I and type III IFNs have prominent roles in OE antiviral functions.

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Obar, Joshua J., Alayna Katherine Caffrey, Xi Wang, et al. "Mda5/MAVS signaling is essential for resistance against Aspergillus fumigatus." Journal of Immunology 200, no. 1_Supplement (2018): 52.23. http://dx.doi.org/10.4049/jimmunol.200.supp.52.23.

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Abstract Type I and III interferons act as important activators of antifungal neutrophil response in the lungs. The RIG-I like receptor (RLR) family, including RIG-I and Mda5, are cytosolic RNA sensors that signal through the MAVS adaptor in order to activate interferon responses against viruses. Whether the RLR family has broader effects on host immunity against other pathogen families remains to be fully explored. Herein we demonstrate that Mda5/MAVS signaling was essential for host resistance against pulmonary Aspergillus fumigatus challenge through the regulation of antifungal leukocyte responses. Aspergillus fumigatus induction of type I interferons was partially dependent on Mda5/MAVS signaling, while type III interferon expression was entirely dependent on Mda5/MAVS signaling. Activation of the interferon pathway was driven by prolonged exposure to fungal spores, rather than germ tubes. Ultimately, interferon signaling drove the expression of CXCL9 and CXCL10, SNPs in the latter are associated with invasive aspergillosis in human patients. Our data suggest a broader role of the RLR family in the regulation of innate immunity to include invasive fungal infections.

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Anes, Elsa, José Miguel Azevedo-Pereira, and David Pires. "Role of Type I Interferons during Mycobacterium tuberculosis and HIV Infections." Biomolecules 14, no. 7 (2024): 848. http://dx.doi.org/10.3390/biom14070848.

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Tuberculosis and AIDS remain two of the most relevant human infectious diseases. The pathogens that cause them, Mycobacterium tuberculosis (Mtb) and HIV, individually elicit an immune response that treads the line between beneficial and detrimental to the host. Co-infection further complexifies this response since the different cytokines acting on one infection might facilitate the dissemination of the other. In these responses, the role of type I interferons is often associated with antiviral mechanisms, while for bacteria such as Mtb, their importance and clinical relevance as a suitable target for manipulation are more controversial. In this article, we review the recent knowledge on how these interferons play distinct roles and sometimes have opposite consequences depending on the stage of the pathogenesis. We highlight the dichotomy between the acute and chronic infections displayed by both infections and how type I interferons contribute to an initial control of each infection individually, while their chronic induction, particularly during HIV infection, might facilitate Mtb primo-infection and progression to disease. We expect that further findings and their systematization will allow the definition of windows of opportunity for interferon manipulation according to the stage of infection, contributing to pathogen clearance and control of immunopathology.

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Su, Helen C., Huie Jing, Yu Zhang, and Jean-Laurent Casanova. "Interfering with Interferons: A Critical Mechanism for Critical COVID-19 Pneumonia." Annual Review of Immunology 41, no. 1 (2023): 561–85. http://dx.doi.org/10.1146/annurev-immunol-101921-050835.

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Infection with SARS-CoV-2 results in clinical outcomes ranging from silent or benign infection in most individuals to critical pneumonia and death in a few. Genetic studies in patients have established that critical cases can result from inborn errors of TLR3- or TLR7-dependent type I interferon immunity, or from preexisting autoantibodies neutralizing primarily IFN-α and/or IFN-ω. These findings are consistent with virological studies showing that multiple SARS-CoV-2 proteins interfere with pathways of induction of, or response to, type I interferons. They are also congruent with cellular studies and mouse models that found that type I interferons can limit SARS-CoV-2 replication in vitro and in vivo, while their absence or diminution unleashes viral growth. Collectively, these findings point to insufficient type I interferon during the first days of infection as a general mechanism underlying critical COVID-19 pneumonia, with implications for treatment and directions for future research.

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Osterlund, Pamela, Taija Pietila, Sergei Kotenko, and Ilkka Julkunen. "Expression of type III lambda interferon genes is showing similar two-wave regulation with type I alpha/beta interferon genes (B50)." Journal of Immunology 178, no. 1_Supplement (2007): LB10—LB11. http://dx.doi.org/10.4049/jimmunol.178.supp.b50.

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Abstract In virus infection the replication of viral genome triggers the expression of antiviral genes, like type I interferons (IFN-alpha/beta), by transcription factors activated through both TLR-dependent and independent pathways. Recently, another class of antiviral type III interferons (IFN-lambda1-3) was identified. Here is presented a detailed characterization of the IFN-lambda1 and IFN-lambda3 gene promoters and functional characterization of virus-specific activation of transcription factors regulating these promoters. Both of these promoters have a functional interferon-stimulated response element (ISRE) and NF-kappaB binding site, although the interferon regulatory factors (IRFs)-binding ISRE was the most crucial regulatory element on these promoters. Ectopic expression of the components of the three virus-induced signaling pathways (MyD88+IRF7, Trif and RIG-I) induced the activation of IFN-lambda1 promoter, whereas the IFN-lambda3 promoter was activated to higher extent only by IRF7 alone or in combination with MyD88. Recently documented IRF3 suppressor Pin1 down-regulated all the three signaling cascades induced IFN promoter activation, but not the NF-kappaB mediated transcription. These results suggest that IFN-lambda1 gene is regulated by both IRF3 and IRF7 like IFN-beta gene, whereas IFN-lambda2/3 genes are induced mainly after IRF7-mediated positive feedback.

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Fernandez-Ruiz, Ruth, and Timothy B. Niewold. "Type I Interferons in Autoimmunity." Journal of Investigative Dermatology 142, no. 3 (2022): 793–803. http://dx.doi.org/10.1016/j.jid.2021.11.031.

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Asselin-Paturel, Carine, and Giorgio Trinchieri. "Production of type I interferons." Journal of Experimental Medicine 202, no. 4 (2005): 461–65. http://dx.doi.org/10.1084/jem.20051395.

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Plasmacytoid dendritic cells (pDCs) are specialized producers of type I interferons (IFNs) that respond to most viruses. Because of their antiviral activity and regulatory functions in innate and adaptive immunity, type I IFNs are important not only for antiviral resistance but also in other types of infections and in immune pathology. Here we discuss recent data that begin to reveal the unique molecular mechanisms underlying the remarkably rapid and efficient type I IFN production by pDCs.

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Balasubramani, Anand. "Type III interferons prime neutrophils." Science 358, no. 6360 (2017): 183.15–185. http://dx.doi.org/10.1126/science.358.6360.183-o.

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Greenberg, Steven A. "Type 1 interferons and myositis." Arthritis Research & Therapy 12, Suppl 1 (2010): S4. http://dx.doi.org/10.1186/ar2885.

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Thaney, Victoria E., and Marcus Kaul. "Type I Interferons in NeuroHIV." Viral Immunology 32, no. 1 (2019): 7–14. http://dx.doi.org/10.1089/vim.2018.0085.

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Greenberg, Steven A. "Dermatomyositis and Type 1 Interferons." Current Rheumatology Reports 12, no. 3 (2010): 198–203. http://dx.doi.org/10.1007/s11926-010-0101-6.

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Wang, Xi, Alayna Katherine Caffrey, Vanessa Espinosa, et al. "Mda5/MAVS are essential for host resistance against Aspergillus fumigatus." Journal of Immunology 204, no. 1_Supplement (2020): 156.15. http://dx.doi.org/10.4049/jimmunol.204.supp.156.15.

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Abstract Type I and III interferons act as important activators of antifungal neutrophil response in the lungs. RIG-I like receptors (RLR) are cytosolic RNA sensors that signal through the MAVS adaptor in order to activate interferon responses against viruses. Whether this pattern-recognition receptor family has broader effects on host immunity against other pathogen families remains to be fully explored. Herein we demonstrate that Mda5/MAVS signaling was essential for host resistance against pulmonary Aspergillus fumigatus challenge through the regulation of antifungal leukocyte responses. Interesting, induction of type I interferons after A. fumigatus challenge was only partially dependent on Mda5/MAVS signaling, while type III interferon expression was entirely dependent on Mda5/MAVS signaling. Ultimately, type I and III interferon signaling drove the expression of CXCL10, which is critical in resistance against invasive aspergillosis in transplant patients. Importantly, we found that polymorphisms in Ifih1 and Mavs were associated with the incidence of invasive pulmonary aspergillosis in a human HSCT cohort. Moreover, polymorphisms in the Ifih1 gene alter the inflammatory response induced in patients with invasive pulmonary aspergillosis, which include interferon-responsive chemokines. In conclusion, our data broaden the role of the RLR family in the regulating innate immunity during infection to include a role in immunity against Aspergillus fumigatus in both mice and humans.

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Riding, Rebecca L., Keitaro Fukuda, Jillian M. Richmond, and John E. Harris. "Suppressing type I interferon enhances both autoimmunity and anti-tumor immunotherapy." Journal of Immunology 198, no. 1_Supplement (2017): 126.11. http://dx.doi.org/10.4049/jimmunol.198.supp.126.11.

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Abstract Vitiligo is an autoimmune disease of the skin in which melanocytes are targeted for destruction by autoreactive CD8 T cells specific for melanocyte/melanoma-shared antigens, such as premelanosome protein (PMEL). We developed a mouse model of vitiligo through adoptive cell transfer (ACT) using PMEL-specific TCR transgenic CD8+ T cells (PMELs) and found that vitiligo pathogenesis is primarily driven by IFNγ. There is much crosstalk between IFNγR signaling and type I interferon signaling as type I interferons, including interferon α and β proteins, can directly regulate shared IFNγ target genes. Therefore, we sought to understand the role of type I interferons in vitiligo. We discovered that type I interferon α-receptor deficient (IFNAR−/−) host mice develop accelerated and more severe vitiligo compared to WT mice. Subsequent studies showed that IFNAR expression was not required on PMELs or the majority of other immune cells to suppress vitiligo, but rather on radioresistant cells. To determine whether this observation could be useful in melanoma immunotherapy, we tested ACT of PMELs in B16F10 melanoma-inoculated IFNAR−/− and WT mice and found that IFNAR−/− mice were relatively protected from the tumor, with a lower tumor burden and an elevated number of tumor-infiltrating PMELs compared to WT mice. Collectively, these results strongly suggest that type I interferon signaling suppresses anti-melanocyte immune responses in both autoimmunity and tumor immunity. We are currently investigating the mechanism of type I interferon suppression, specifically what cell types are driving this response and what mediators are involved.

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Siu, Kam-Leung, Kin-Hang Kok, Ming-Him James Ng та ін. "Severe Acute Respiratory Syndrome Coronavirus M Protein Inhibits Type I Interferon Production by Impeding the Formation of TRAF3·TANK·TBK1/IKKϵ Complex". Journal of Biological Chemistry 284, № 24 (2009): 16202–9. http://dx.doi.org/10.1074/jbc.m109.008227.

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Severe acute respiratory syndrome (SARS) coronavirus is highly pathogenic in humans and evades innate immunity at multiple levels. It has evolved various strategies to counteract the production and action of type I interferons, which mobilize the front-line defense against viral infection. In this study we demonstrate that SARS coronavirus M protein inhibits gene transcription of type I interferons. M protein potently antagonizes the activation of interferon-stimulated response element-dependent transcription by double-stranded RNA, RIG-I, MDA5, TBK1, IKKϵ, and virus-induced signaling adaptor (VISA) but has no influence on the transcriptional activity of this element when IRF3 or IRF7 is overexpressed. M protein physically associates with RIG-I, TBK1, IKKϵ, and TRAF3 and likely sequesters some of them in membrane-associated cytoplasmic compartments. Consequently, the expression of M protein prevents the formation of TRAF3·TANK·TBK1/IKKϵ complex and thereby inhibits TBK1/IKKϵ-dependent activation of IRF3/IRF7 transcription factors. Taken together, our findings reveal a new mechanism by which SARS coronavirus circumvents the production of type I interferons.

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Moley, Charles R., Catherine Chambers, Alexis Dadelahi, et al. "Innate lymphoid cells and interferons limit neurologic complications of Brucellosis." Journal of Immunology 210, no. 1_Supplement (2023): 81.16. http://dx.doi.org/10.4049/jimmunol.210.supp.81.16.

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Abstract Brucellosis is a globally significant zoonotic disease. Human brucellosis patients develop flu-like symptoms and focal complications including arthritis and neurobrucellosis. The purpose of our study was to uncover the role of innate lymphoid cells (ILCs) in the pathogenesis of focal brucellosis. After footpad infection, we found NK cells and ILC1 cells both limit joint colonization by Brucella. Mice lacking NK cells, and in particular mice lacking all ILCs also developed marked arthritis after footpad infection. Following pulmonary infection, mice lacking adaptive immune cells and ILCs developed arthritis, neurologic complications, and meningitis. Adaptive immune cells and ILCs both limited colonization of the brain by Brucella following pulmonary infection. Transcriptional analysis of Brucella-infected brains revealed marked upregulation of genes associated with inflammation and interferon responses, as well as downregulation of genes associated with neurologic function. Type II interferon deficiency resulted in colonization of the brain by Brucella, but mice lacking both type I and type II interferon signaling more rapidly developed clinical signs of neurobrucellosis, exhibited hippocampal neuronal loss, and had higher levels of Brucella in their brains than mice lacking type II interferon signaling alone. Collectively, our findings indicate ILCs and interferons play an important role in prevention of focal complications during Brucella infection, and that mice with deficiencies in ILCs or interferons can be used to study pathogenesis of neurobrucellosis. Supported by grants from NIH (T32 OD011126-4, R21 AI153074-02)

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Billiau, A. "Interferon beta in the cytokine network: an anti-inflammatory pathway." Multiple Sclerosis Journal 1, no. 1_suppl (1995): S2—S4. https://doi.org/10.1177/1352458519950101002.

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Interferons are cytokines and thus fulfil a vital role in communication between cells in their microenvironment Type I interferons, the group to which interferon beta (IFN-β) belongs, share several structural and functional properties by which they distinguish themselves from type II interferon or IFN-y. In particular, IFN-β can be produced by many different cells while IFN-y is an exclusively lymphocytic cytokine, i.e. a lymphokine. IFN-β is functionally linked to other cytokines as it can be induced by some of them (e.g. interleukin I) and as its actions can be potentiated or antagonized by other cytokines. Such interactions can take place at several levels, e.g. at the level of signal transduction and transcription activation. Of potential interest for the role of IFN-β in multiple sclerosis is its ability to function as a deactivator of mononuclear phagocytes, and hence as an inhibitor of inflammation.

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Chen, Mengying, Jingyun Hu, Xinni Zhou, et al. "Long Non-Coding RNA THRIL Promotes Influenza Virus Replication by Inhibiting the Antiviral Innate Immune Response." Viruses 17, no. 2 (2025): 153. https://doi.org/10.3390/v17020153.

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Long non-coding RNAs (lncRNAs) have been recognized for their crucial roles in the replication processes of various viruses. However, the specific functions and regulatory mechanisms of many lncRNAs in influenza A virus (IAV) pathogenesis remain poorly understood. In this study, we identified lncRNA THRIL and observed a significant reduction in its expression following IAV infection in A549 cells. The treatment of cells with the viral mimic poly (I:C), or with type I and type III interferons, resulted in a substantial decrease in THRIL expression. Furthermore, THRIL overexpression significantly enhanced IAV replication, while its silencing markedly reduced IAV replication. Additionally, IAV infection led to notable reductions in the expression levels of type I and type III interferons in cell lines overexpressing THRIL compared to control groups; conversely, cell lines with THRIL knockdown exhibited significantly higher interferon levels than control groups. Moreover, THRIL was found to inhibit the expression of several critical interferon-stimulated genes (ISGs), which are essential for an effective antiviral response. Notably, our findings demonstrated that THRIL impaired the activation of IRF3, a key transcription factor in the interferon signaling pathway, thereby suppressing host innate immunity. These results highlight THRIL’s potential as a therapeutic target for antiviral strategies.

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Saranya, S. R., and R. Sudhakaran. "A mini review of Tilapia Lake Virus (TiLV): Disease pathogenesis and host immune response against virus." Research Journal of Biotechnology 19, no. 8 (2024): 105–11. http://dx.doi.org/10.25303/1908rjbt1050111.

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The use of tilapia for farming is increasing every year to meet the worldwide demand for protein sources. Unexpectedly, high mortality rates of tilapia, known as tilapia lake virus (TiLV), have been observed in various countries, including India. TiLV is a pathogenic virus with a trilaminar capsid that is composed of a negative-sense icosahedral RNA virus. Infected tilapia exhibit noticeable signs and symptoms, indicating the presence of the disease. Understanding TiLV is crucial for effective preventing of its spread in the tilapia farming industry. Interferons can hinder viral particles by inhibiting viral replication in the host. These bony fish species require type I and III interferons to protect against the virus. Type I interferons act against all nucleated cells, while type III interferons specifically target dendritic and epithelial cells. Interferon-stimulating gene (ISG) expression, induced by signaling molecules, blocks the virus from spreading to other cells. In vertebrates, the type I IFN-inducible gene product 'Mx' has demonstrated high resistance to orthomyxovirus infection. Recent findings suggest that TiLV lacks HA ligands for binding to the Sia receptor. Protein kinase (PKR), an integral component of the innate immune response, is considered the first-line defense molecule against viral infection in fish. When the viral pathogen enters the host cell, PKR is activated by dsRNA and phosphorylates the translation initiation factor eIF2α, triggering an innate immune response activated by type I interferon. The host immune response to pathogens is also regulated by cytokines which effectively induce inflammation during TiLV infection. Recent research has shown that intraperitoneally injected zebrafish are susceptible to TiLV infection. Therefore, zebrafish were chosen as a model organism for studying the immune response against TiLV. Zebrafish possess a well-developed immune system that allows for the study of both innate and humoral immunity, providing insights into the antiviral activity of both the host and the pathogen. There is limited understanding of the structure of the virus and minimal information on the immunopathogenesis of TiLV. Therefore, a comprehensive understanding of disease strategies is necessary to develop solution to this epidemic.

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Tilton, John C., Maura M. Manion, Marlise R. Luskin, et al. "Human Immunodeficiency Virus Viremia Induces Plasmacytoid Dendritic Cell Activation In Vivo and Diminished Alpha Interferon Production In Vitro." Journal of Virology 82, no. 8 (2008): 3997–4006. http://dx.doi.org/10.1128/jvi.01545-07.

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ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection has been associated with perturbations of plasmacytoid dendritic cells (PDC), including diminished frequencies in the peripheral blood and reduced production of type I interferons (IFNs) in response to in vitro stimulation. However, recent data suggest a paradoxical increase in production of type 1 interferons in vivo in HIV-infected patients compared to uninfected controls. Using a flow cytometric assay to detect IFN-α-producing cells within unseparated peripheral blood mononuclear cells, we observed that short-term interruptions of antiretroviral therapy are sufficient to result in significantly reduced IFN-α production by PDC in vitro in response to CpG A ligands or inactivated HIV particles. The primary cause of diminished IFN-α production was reduced responsiveness of PDC to de novo stimulation, not diminished per cell IFN-α production or migration of cells to lymphoid organs. Real-time PCR analysis of purified PDC from patients prior to and during treatment interruptions revealed that active HIV-1 replication is associated with upregulation of type I IFN-stimulated gene expression. Treatment of hepatitis C virus-infected patients with IFN-α2b and ribavirin for hepatitis C virus infection resulted in a profound suppression of de novo IFN-α production in response to CpG A or inactivated HIV particles, similar to the response observed in HIV-infected patients. Together, these results suggest that diminished production of type I interferons in vitro by PDC from HIV-1-infected patients may not represent diminished interferon production in vivo. Rather, diminished function in vitro is likely a consequence of prior activation via type I interferons or HIV virions in vivo.

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WOO, JIN SEOK, Sonal Srikanth, Beibei Wu, et al. "The Ca2+ sensor STIM1 regulates the type I interferon response by retaining the signaling adaptor STING at the endoplasmic reticulum." Journal of Immunology 202, no. 1_Supplement (2019): 63.3. http://dx.doi.org/10.4049/jimmunol.202.supp.63.3.

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Abstract Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER) signaling adaptor that is essential for the type I interferon response to DNA pathogens. Aberrant activation of STING is linked to the pathology of autoimmune and autoinflammatory diseases. The rate-limiting step for the activation of STING is its translocation from the ER to the ER-Golgi intermediate compartment. Here, we found that deficiency in the Ca2+ sensor stromal interaction molecule 1 (STIM1) caused spontaneous activation of STING and enhanced expression of type I interferons under resting conditions in mice and a patient with combined immunodeficiency. Mechanistically, STIM1 associated with STING to retain it in the ER membrane, and coexpression of full-length STIM1 or a STING-interacting fragment of STIM1 suppressed the function of dominant STING mutants that cause autoinflammatory diseases. Furthermore, deficiency in STIM1 strongly enhanced the expression of type I interferons after viral infection and prevented the lethality of infection with a DNA virus in vivo. This work delineates a STIM1-STING circuit that maintains the resting state of the STING pathway.

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Meloni, Antonella, Maria Furcas, Filomena Cetani, et al. "Autoantibodies against Type I Interferons as an Additional Diagnostic Criterion for Autoimmune Polyendocrine Syndrome Type I." Journal of Clinical Endocrinology & Metabolism 93, no. 11 (2008): 4389–97. http://dx.doi.org/10.1210/jc.2008-0935.

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Context: In autoimmune polyendocrinopathy syndrome type I (APS-I), mutations in the autoimmune regulator gene (AIRE) impair thymic self-tolerance induction in developing T cells. The ensuing autoimmunity particularly targets ectodermal and endocrine tissues, but chronic candidiasis usually comes first. We recently reported apparently APS-I-specific high-titer neutralizing autoantibodies against type I interferons in 100% of Finnish and Norwegian patients, mainly with two prevalent AIRE truncations. Objectives: Because variability in clinical features and age at onset in APS-I frequently results in unusual presentations, we prospectively checked the diagnostic potential of anti-interferon antibodies in additional APS-I panels with other truncations or rare missense mutations and in disease controls with chronic mucocutaneous candidiasis (CMC) but without either common AIRE mutation. Design: The study was designed to detect autoantibodies against interferon-α2 and interferon-ω in antiviral neutralization assays. Setting and Patients: Patients included 14 British/Irish, 15 Sardinian, and 10 Southern Italian AIRE-mutant patients with APS-I; also 19 other patients with CMC, including four families with cosegregating thyroid autoimmunity. Outcome: The diagnostic value of anti-interferon autoantibodies was assessed. Results: We found antibodies against interferon-α2 and/or interferon-ω in all 39 APS-I patients vs. zero of 48 unaffected relatives and zero of 19 British/Irish CMC patients. Especially against interferon-ω, titers were nearly always high, regardless of the exact APS-I phenotype/duration or AIRE genotype, including 12 different AIRE length variants or 10 point substitutions overall (n = 174 total). Strikingly, in one family with few typical APS-I features, these antibodies cosegregated over three generations with autoimmune hypothyroidism plus a dominant-negative G228W AIRE substitution. Conclusions: Otherwise restricted to patients with thymoma and/or myasthenia gravis, these precocious persistent antibodies show 98% or higher sensitivity and APS-I specificity and are thus a simpler diagnostic option than detecting AIRE mutations.

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Nagabhushan, Tattanahalli L., Paul Reichert, Mark R. Walter, and Nicholas J. Murgolo. "Type I interferon structures: Possible scaffolds for the interferon-alpha receptor complex." Canadian Journal of Chemistry 80, no. 8 (2002): 1166–73. http://dx.doi.org/10.1139/v02-158.

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The structures of several type I interferons (IFNs) are known. We review the structural information known for IFN alphas and compare them to other interferons and cytokines. We also review the structural information known or proposed for IFNcell receptor complexes. However, the structure of the IFN cell receptor IFN receptor2 (IFNAR2) and IFN receptor1 (IFNAR1) complex has not yet been determined. This paper describes a structural model of human IFN-IFNAR2/IFNAR1 complex using human IFN-α2b dimer as the ligand. Both the structures of recombinant human IFN-α2b and IFN-β were determined by X-ray crystallography as zinc-mediated dimers. Our proposed model was generated using human IFN-α2b dimer docked with IFNAR2/IFNAR1. We compare our model with the receptor complex models proposed for IFN-β and IFN-γ to contrast similarities and differences. The mutual binding sites of human IFN-α2b and IFNAR2/IFNAR1 complex are consistent with available mutagenesis studies.Key words: three dimensional structure, antiviral activity, receptor, interferon.

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Rioux, Bastien, Michael Chong, Rosie Walker, et al. "Phenotypes associated with genetic determinants of type I interferon regulation in the UK Biobank: a protocol." Wellcome Open Research 8 (November 23, 2023): 550. http://dx.doi.org/10.12688/wellcomeopenres.20385.1.

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Background Type I interferons are cytokines involved in innate immunity against viruses. Genetic disorders of type I interferon regulation are associated with a range of autoimmune and cerebrovascular phenotypes. Carriers of pathogenic variants involved in genetic disorders of type I interferons are generally considered asymptomatic. Preliminary data suggests, however, that genetically determined dysregulation of type I interferon responses is associated with autoimmunity, and may also be relevant to sporadic cerebrovascular disease and dementia. We aim to determine whether functional variants in genes involved in type I interferon regulation and signalling are associated with the risk of autoimmunity, stroke, and dementia in a population cohort. Methods We will perform a hypothesis-driven candidate pathway association study of type I interferon-related genes using rare variants in the UK Biobank (UKB). We will manually curate type I interferon regulation and signalling genes from a literature review and Gene Ontology, followed by clinical and functional filtering. Variants of interest will be included based on pre-defined clinical relevance and functional annotations (using LOFTEE, M-CAP and a minor allele frequency <0.1%). The association of variants with 15 clinical and three neuroradiological phenotypes will be assessed with a rare variant genetic risk score and gene-level tests, using a Bonferroni-corrected p-value threshold from the number of genetic units and phenotypes tested. We will explore the association of significant genetic units with 196 additional health-related outcomes to help interpret their relevance and explore the clinical spectrum of genetic perturbations of type I interferon. Ethics and dissemination The UKB has received ethical approval from the North West Multicentre Research Ethics Committee, and all participants provided written informed consent at recruitment. This research will be conducted using the UKB Resource under application number 93160. We expect to disseminate our results in a peer-reviewed journal and at an international cardiovascular conference.

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Suprunenko, Tamara, and Markus Hofer. "Complexities of Type I Interferon Biology: Lessons from LCMV." Viruses 11, no. 2 (2019): 172. http://dx.doi.org/10.3390/v11020172.

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Over the past decades, infection of mice with lymphocytic choriomeningitis virus (LCMV) has provided an invaluable insight into our understanding of immune responses to viruses. In particular, this model has clarified the central roles that type I interferons play in initiating and regulating host responses. The use of different strains of LCMV and routes of infection has allowed us to understand how type I interferons are critical in controlling virus replication and fostering effective antiviral immunity, but also how they promote virus persistence and functional exhaustion of the immune response. Accordingly, these discoveries have formed the foundation for the development of novel treatments for acute and chronic viral infections and even extend into the management of malignant tumors. Here we review the fundamental insights into type I interferon biology gained using LCMV as a model and how the diversity of LCMV strains, dose, and route of administration have been used to dissect the molecular mechanisms underpinning acute versus persistent infection. We also identify gaps in the knowledge regarding LCMV regulation of antiviral immunity. Due to its unique properties, LCMV will continue to remain a vital part of the immunologists’ toolbox.

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KUILYA, SANTANU. "Interferons during HSV-2 Infection: Immune Regulation." INTERANTIONAL JOURNAL OF SCIENTIFIC RESEARCH IN ENGINEERING AND MANAGEMENT 08, no. 02 (2024): 1–13. http://dx.doi.org/10.55041/ijsrem28707.

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Herpes simplex virus type 2 (HSV-2) infection is a prevalent sexually transmitted infection that disproportionately affects women worldwide. Currently, there are no vaccines or curative treatments available, leading to life-long infections. During HSV-2 infection, interferons (IFNs) play a crucial role in the body's antiviral defense. Type I IFNs (IFN-alpha and IFN-beta) and type III IFNs (IFN-lambda) are produced by host cells in response to the virus, alerting neighboring cells to its presence and inducing an antiviral state that limits viral replication and spread. Type III IFNs, produced in epithelial cells, also contribute to controlling viral replication in mucosal tissues. However, HSV-2 has evolved strategies to evade IFN-induced responses, allowing the virus to partially escape the host's immune response, establish latency, and cause recurrent infections. The delicate balance between the host's IFN response and the virus's immune evasion mechanisms determines the outcome of HSV-2 infection. Understanding the intricate interplay between HSV-2 and interferon signalling is critical for developing effective therapies and vaccines to combat this sexually transmitted infection. Keywords: HSV-2, Interferons, Innate immunity, Immune regulation

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Sozzani, Silvano, Daniela Bosisio, Mirko Scarsi, and Angela Tincani. "Type I interferons in systemic autoimmunity." Autoimmunity 43, no. 3 (2010): 196–203. http://dx.doi.org/10.3109/08916930903510872.

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David, Michael. "Signal Transduction by Type I Interferons." BioTechniques 33, no. 4S (2002): S58—S65. http://dx.doi.org/10.2144/oct0207.

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Doly, J., A. Civas, S. Navarro, and G. Uze. "Type I interferons: expression and signalization." Cellular and Molecular Life Sciences CMLS 54, no. 10 (1998): 1109–21. http://dx.doi.org/10.1007/s000180050240.

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Stetson, Daniel B., and Ruslan Medzhitov. "Type I Interferons in Host Defense." Immunity 25, no. 3 (2006): 373–81. http://dx.doi.org/10.1016/j.immuni.2006.08.007.

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Viscomi, Giuseppe C. "Structure-activity of type I interferons." Biotherapy 10, no. 1 (1997): 59–86. http://dx.doi.org/10.1007/bf02678218.

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Yao, Yihong, Zheng Liu, Bahija Jallal, Nan Shen, and Lars Rönnblom. "Type I interferons in Sjögren's syndrome." Autoimmunity Reviews 12, no. 5 (2013): 558–66. http://dx.doi.org/10.1016/j.autrev.2012.10.006.

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Journal articles on the topic 'Type I interferons'

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