scholarly journals Complexities of Type I Interferon Biology: Lessons from LCMV

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 172 ◽  
Author(s):  
Tamara Suprunenko ◽  
Markus Hofer
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Type I Interferon ◽  
Malignant Tumors ◽  
Antiviral Immunity ◽  
Lymphocytic Choriomeningitis ◽  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Novel Treatments

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.

scholarly journals Type I Interferon at the Interface of Antiviral Immunity and Immune Regulation: The Curious Case of HIV-1

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-20 ◽  
Author(s):  
Adriano Boasso
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Type I Interferon ◽  
Critical Role ◽  
Antiviral Immunity ◽  
Target Cells ◽  
Type I ◽  
Cell Immunity ◽  
Hiv 1

Type I interferon (IFN-I) play a critical role in the innate immune response against viral infections. They actively participate in antiviral immunity by inducing molecular mechanisms of viral restriction and by limiting the spread of the infection, but they also orchestrate the initial phases of the adaptive immune response and influence the quality of T cell immunity. During infection with the human immunodeficiency virus type 1 (HIV-1), the production of and response to IFN-I may be severely altered by the lymphotropic nature of the virus. In this review I consider the different aspects of virus sensing, IFN-I production, signalling, and effects on target cells, with a particular focus on the alterations observed following HIV-1 infection.

scholarly journals Crosstalk between Autophagy and Type I Interferon Responses in Innate Antiviral Immunity

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 132 ◽  
Author(s):  
Yu Tian ◽  
Ming-Li Wang ◽  
Jun Zhao
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Type I Interferon ◽  
Antiviral Immunity ◽  
Type I ◽  
Viral Components ◽  
Interferon Responses ◽  
Innate Antiviral Immunity

Autophagy exhibits dual effects during viral infections, promoting the clearance of viral components and activating the immune system to produce antiviral cytokines. However, some viruses impair immune defenses by collaborating with autophagy. Mounting evidence suggests that the interaction between autophagy and innate immunity is critical to understanding the contradictory roles of autophagy. Type I interferon (IFN-I) is a crucial antiviral factor, and studies have indicated that autophagy affects IFN-I responses by regulating IFN-I and its receptors expression. Similarly, IFN-I and interferon-stimulated gene (ISG) products can harness autophagy to regulate antiviral immunity. Crosstalk between autophagy and IFN-I responses could be a vital aspect of the molecular mechanisms involving autophagy in innate antiviral immunity. This review briefly summarizes the approaches by which autophagy regulates antiviral IFN-I responses and highlights the recent advances on the mechanisms by which IFN-I and ISG products employ autophagy against viruses.

scholarly journals SARS-CoV-2 infection in the Syrian hamster model causes inflammation as well as type I interferon dysregulation in both respiratory and non-respiratory tissues including the heart and kidney

2021 ◽  
Author(s):  
Magen E. Francis ◽  
Una Goncin ◽  
Andrea Kroeker ◽  
Cynthia Swan ◽  
Robyn Ralph ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Clinical Symptoms ◽  
Type I Interferons ◽  
Host Responses ◽  
Type I ◽  
Hamster Model ◽  
Organ Systems ◽  
Major Organ ◽  
Kidney Liver ◽  
Multiorgan Disease

AbstractCOVID-19 (coronavirus disease 2019) caused SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of mycarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).

scholarly journals How fragile we are. Influence of STimulator of INterferon Genes, STING, variants on pathogen recognition and immune response efficiency

2021 ◽  
Author(s):  
Jeremy Morere ◽  
Cecilia Hognon ◽  
Tom Miclot ◽  
Tao Jiang ◽  
Elise Dumont ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Dynamical Behavior ◽  
Structural Features ◽  
Type I Interferons ◽  
Machine Learning Techniques ◽  
Type I ◽  
Interaction Patterns

The STimulator of INterferon Genes (STING) protein is a cornerstone of the human immune response. Its activation by cGAMP upon the presence of cytosolic DNA stimulates the production of type I interferons and inflammatory cytokines which are crucial for protecting cells from infections. STING signaling pathway can also influence both tumor-suppressive and tumor-promoting mechanisms, rendering it an appealing target for drug design. In the human population, several STING variants exist and exhibit dramatic differences in their activity, impacting the efficiency of the host defense against infections. Understanding the differential molecular mechanisms exhibited by these variants is of utmost importance notably towards personalized medicine treatments against diseases such as viral infections (COVID-19, Dengue...), cancers, or auto-inflammatory diseases. Owing to micro-seconds scale molecular modeling simulations and post-processing by contacts analysis and Machine Learning techniques, we reveal the dynamical behavior of four STING variants (wild type, G230A, R293Q, and G230A-R293Q) and we rationalize the variability of efficiency observed experimentally. Our results show that the decrease of STING activity is linked to a stiffening of key-structural features of the binding cavity, together with changes of the interaction patterns within the protein.

scholarly journals Mechanisms of type I interferon action and its role in infections and diseases transmission in mammals

2017 ◽  
Vol 64 (2) ◽  
Author(s):  
Weronika Ratajczak ◽  
Paulina Niedźwiedzka-Rystwej ◽  
Beata Tokarz-Deptuła ◽  
Wiesław Deptuła
Keyword(s):  
Signaling Pathways ◽  
Crucial Role ◽  
Viral Infections ◽  
Type I Interferon ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Stimulated Genes

Interferons (IFN) are pivotal regulators of immunological processes. The paper describes mainly type I interferons -α and –β and its recently recounted signaling pathways, especially ISG – interferon stimulated genes, having a crucial role in regulating IFN recruitment. Moreover, the paper shows the data on the role of interferons -α and –β in infections – not only commonly known viral infections, but also bacterial, fungal and parasitic. 

scholarly journals Human Type I Interferon Antiviral Effects in Respiratory and Reemerging Viral Infections

2020 ◽  
Vol 2020 ◽  
pp. 1-27 ◽  
Author(s):  
Patricio L. Acosta ◽  
Alana B. Byrne ◽  
Diego R. Hijano ◽  
Laura B. Talarico
Keyword(s):  
Immune System ◽  
Host Defense ◽  
Immune Modulation ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Current Knowledge ◽  
Type I Interferons ◽  
Type I ◽  
Antiviral Effects ◽  
Wide Range

Type I interferons (IFN-I) are a group of related proteins that help regulate the activity of the immune system and play a key role in host defense against viral infections. Upon infection, the IFN-I are rapidly secreted and induce a wide range of effects that not only act upon innate immune cells but also modulate the adaptive immune system. While IFN-I and many IFN stimulated genes are well-known for their protective antiviral role, recent studies have associated them with potential pathogenic functions. In this review, we summarize the current knowledge regarding the complex effects of human IFN-I responses in respiratory as well as reemerging flavivirus infections of public health significance and the molecular mechanisms by which viral proteins antagonize the establishment of an antiviral host defense. Antiviral effects and immune modulation of IFN-stimulated genes is discussed in resisting and controlling pathogens. Understanding the mechanisms of these processes will be crucial in determining how viral replication can be effectively controlled and in developing safe and effective vaccines and novel therapeutic strategies.

scholarly journals When human guanylate-binding proteins meet viral infections

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Rongzhao Zhang ◽  
Zhixin Li ◽  
Yan-Dong Tang ◽  
Chenhe Su ◽  
Chunfu Zheng
Keyword(s):  
Innate Immunity ◽  
Viral Infection ◽  
Binding Proteins ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Downstream Signaling ◽  
Antiviral Innate Immunity

AbstractInnate immunity is the first line of host defense against viral infection. After invading into the cells, pathogen-associated-molecular-patterns derived from viruses are recognized by pattern recognition receptors to activate the downstream signaling pathways to induce the production of type I interferons (IFN-I) and inflammatory cytokines, which play critical functions in the host antiviral innate immune responses. Guanylate-binding proteins (GBPs) are IFN-inducible antiviral effectors belonging to the guanosine triphosphatases family. In addition to exerting direct antiviral functions against certain viruses, a few GBPs also exhibit regulatory roles on the host antiviral innate immunity. However, our understanding of the underlying molecular mechanisms of GBPs' roles in viral infection and host antiviral innate immune signaling is still very limited. Therefore, here we present an updated overview of the functions of GBPs during viral infection and in antiviral innate immunity, and highlight discrepancies in reported findings and current challenges for future studies, which will advance our understanding of the functions of GBPs and provide a scientific and theoretical basis for the regulation of antiviral innate immunity.

scholarly journals Crosstalk Between Mammalian Antiviral Pathways

2019 ◽  
Vol 5 (1) ◽  
pp. 29 ◽  
Author(s):  
Samir Watson ◽  
Lisanne Knol ◽  
Jeroen Witteveldt ◽  
Sara Macias
Keyword(s):  
Small Rna ◽  
Mammalian Cells ◽  
Viral Infections ◽  
Type I Interferon ◽  
Innate Immune ◽  
Type I Interferons ◽  
Interferon Response ◽  
Classical Type ◽  
Type I ◽  
Rna Biogenesis

As part of their innate immune response against viral infections, mammals activate the expression of type I interferons to prevent viral replication and dissemination. An antiviral RNAi-based response can be also activated in mammals, suggesting that several mechanisms can co-occur in the same cell and that these pathways must interact to enable the best antiviral response. Here, we will review how the classical type I interferon response and the recently described antiviral RNAi pathways interact in mammalian cells. Specifically, we will uncover how the small RNA biogenesis pathway, composed by the nucleases Drosha and Dicer can act as direct antiviral factors, and how the type-I interferon response regulates the function of these. We will also describe how the factors involved in small RNA biogenesis and specific small RNAs impact the activation of the type I interferon response and antiviral activity. With this, we aim to expose the complex and intricate network of interactions between the different antiviral pathways in mammals.

scholarly journals Manipulation of Type I Interferon Signaling by HIV and AIDS-Associated Viruses

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Buyuan He ◽  
James T. Tran ◽  
David Jesse Sanchez
Keyword(s):  
Viral Infections ◽  
Type I Interferon ◽  
Antiviral Effect ◽  
Hiv And Aids ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Signaling ◽  
Chronic Viral Infections ◽  
Pathogenic Viruses ◽  
The Impact

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.

scholarly journals The Pathogenesis, Molecular Mechanisms and Therapeutic Potential of the Interferon Pathway in Systemic Lupus Erythematosus and Other Autoimmune Diseases

2021 ◽  
Vol 22 (20) ◽  
pp. 11286
Author(s):  
Madhu Ramaswamy ◽  
Raj Tummala ◽  
Katie Streicher ◽  
Andre Nogueira da Costa ◽  
Philip. Z. Brohawn
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Molecular Mechanisms ◽  
Type I Interferon ◽  
Type I Interferons ◽  
Type I ◽  
Systemic Lupus ◽  
Disease Etiology ◽  
Interferon Pathway

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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