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 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 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 Synthetic rewiring and boosting type I interferon responses for visualization and counteracting viral infections

2020 ◽  
Vol 48 (20) ◽  
pp. 11799-11811
Author(s):  
Natascha Gödecke ◽  
Jan Riedel ◽  
Sabrina Herrmann ◽  
Sara Behme ◽  
Ulfert Rand ◽  
...  
Keyword(s):  
Positive Feedback ◽  
Viral Infections ◽  
Type I Interferon ◽  
Type I ◽  
First Line ◽  
Initial Stimulus ◽  
Sensor Actuator ◽  
Actuator System ◽  
Interferon Responses ◽  
Robust Sensing

Abstract Mammalian first line of defense against viruses is accomplished by the interferon (IFN) system. Viruses have evolved numerous mechanisms to reduce the IFN action allowing them to invade the host and/or to establish latency. We generated an IFN responsive intracellular hub by integrating the synthetic transactivator tTA into the chromosomal Mx2 locus for IFN-based activation of tTA dependent expression modules. The additional implementation of a synthetic amplifier module with positive feedback even allowed for monitoring and reacting to infections of viruses that can antagonize the IFN system. Low and transient IFN amounts are sufficient to trigger these amplifier cells. This gives rise to higher and sustained—but optionally de-activatable—expression even when the initial stimulus has faded out. Amplification of the IFN response induced by IFN suppressing viruses is sufficient to protect cells from infection. Together, this interfaced sensor/actuator system provides a toolbox for robust sensing and counteracting viral infections.

scholarly journals PTEN-L promotes type I interferon responses and antiviral immunity

2017 ◽  
Vol 15 (1) ◽  
pp. 48-57 ◽  
Author(s):  
Yuanyuan Cao ◽  
Hongyun Wang ◽  
Liu Yang ◽  
Zhen Zhang ◽  
Chenlin Li ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Antiviral Immunity ◽  
Type I ◽  
Interferon Responses

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 Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses

PLoS Biology ◽  
2017 ◽  
Vol 15 (12) ◽  
pp. e2004086 ◽  
Author(s):  
Andrew E. Shaw ◽  
Joseph Hughes ◽  
Quan Gu ◽  
Abdelkader Behdenna ◽  
Joshua B. Singer ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Type I Interferon ◽  
Innate Immune ◽  
Type I ◽  
Fundamental Properties ◽  
Interferon Responses

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 Role of NLRs in the Regulation of Type I Interferon Signaling, Host Defense and Tolerance to Inflammation

2021 ◽  
Vol 22 (3) ◽  
pp. 1301
Author(s):  
Ioannis Kienes ◽  
Tanja Weidl ◽  
Nora Mirza ◽  
Mathias Chamaillard ◽  
Thomas A. Kufer
Keyword(s):  
Viral Infections ◽  
Type I Interferon ◽  
Tissue Injury ◽  
Interferon Response ◽  
Type I ◽  
Interferon Signaling ◽  
Microbial Products ◽  
Interferon Responses

Type I interferon signaling contributes to the development of innate and adaptive immune responses to either viruses, fungi, or bacteria. However, amplitude and timing of the interferon response is of utmost importance for preventing an underwhelming outcome, or tissue damage. While several pathogens evolved strategies for disturbing the quality of interferon signaling, there is growing evidence that this pathway can be regulated by several members of the Nod-like receptor (NLR) family, although the precise mechanism for most of these remains elusive. NLRs consist of a family of about 20 proteins in mammals, which are capable of sensing microbial products as well as endogenous signals related to tissue injury. Here we provide an overview of our current understanding of the function of those NLRs in type I interferon responses with a focus on viral infections. We discuss how NLR-mediated type I interferon regulation can influence the development of auto-immunity and the immune response to infection.

scholarly journals Thogoto Virus Infection Induces Sustained Type I Interferon Responses That Depend on RIG-I-Like Helicase Signaling of Conventional Dendritic Cells

2010 ◽  
Vol 84 (23) ◽  
pp. 12344-12350 ◽  
Author(s):  
Georg Kochs ◽  
Stefanie Bauer ◽  
Carola Vogt ◽  
Theresa Frenz ◽  
Jürg Tschopp ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Host Defense ◽  
Viral Infections ◽  
Type I Interferon ◽  
Type I ◽  
Type I Ifn ◽  
Toll Like Receptor ◽  
Tlr Signaling ◽  
The Matrix ◽  
Interferon Responses

ABSTRACT Type I interferon (IFN-α/β) induction upon viral infection contributes to the early antiviral host defense and ensures survival until the onset of adaptive immunity. Many viral infections lead to an acute, transient IFN expression which peaks a few hours after infection and reverts to initial levels after 24 to 36 h. Robust IFN expression often is conferred by specialized plasmacytoid dendritic cells (pDC) and may depend on positive-feedback amplification via the type I IFN receptor (IFNAR). Here, we show that mice infected with Thogoto virus (THOV), which is an influenza virus-like orthomyxovirus transmitted by ticks, mounted sustained IFN responses that persisted up to 72 h after infection. For this purpose, we used a variant of THOV lacking its IFN-antagonistic protein ML, an elongated version of the matrix (M) protein [THOV(ΔML)]. Of note, large amounts of type I IFN were also found in the serum of mice lacking the IFNAR. Early IFN-α expression seemed to depend on Toll-like receptor (TLR) signaling, whereas prolonged IFN-α responses strictly depended on RIG-I-like helicase (RLH) signaling. Unexpectedly, THOV(ΔML)-infected bone marrow-derived pDC (BM-pDC) produced only moderate IFN levels, whereas myeloid DC (BM-mDC) showed massive IFN induction that was IPS-1-dependent, suggesting that BM-mDC are involved in the massive, sustained IFN production in THOV(ΔML)-infected animals. Thus, our data are compatible with the model that THOV(ΔML) infection is sensed in the acute phase via TLR and RLH systems, whereas at later time points only RLH signaling is responsible for the induction of sustained IFN responses.

scholarly journals Loss of mitochondrial protease CLPP activates type I interferon responses through the mtDNA-cGAS-STING signaling axis

2020 ◽  
Author(s):  
Sylvia Torres-Odio ◽  
Yuanjiu Lei ◽  
Suzana Gispert ◽  
Antonia Maletzko ◽  
Jana Key ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Type I Interferon ◽  
Type I ◽  
Signaling Axis ◽  
Perrault Syndrome ◽  
Immune Pathway ◽  
Interferon Responses ◽  
Antiviral Gene ◽  
Innate Immune Pathway

AbstractCaseinolytic mitochondrial matrix peptidase proteolytic subunit, CLPP, is a serine protease that degrades damaged or misfolded mitochondrial proteins. CLPP null mice exhibit growth retardation, deafness, and sterility, resembling human Perrault syndrome (PS), but also display immune system alterations. However, the molecular mechanisms and signaling pathways underlying immunological changes in CLPP null mice remain unclear. Here we report the steady state activation of type I interferon (IFN-I) signaling and antiviral gene expression in CLPP deficient cells and tissues. Depletion of the cyclic GMP-AMP (cGAS)-Stimulator of Interferon Genes (STING) DNA sensing pathway ablates heightened IFN-I responses and abrogates the broad viral resistance phenotype of CLPP null cells. Moreover, we report that CLPP deficiency leads to mitochondrial DNA (mtDNA) instability and packaging alterations. Pharmacological and genetic approaches to deplete mtDNA or inhibit cytosolic release markedly reduce antiviral gene expression, implicating mtDNA stress as the driver of IFN-I signaling in CLPP null mice. Our work places the cGAS-STING-IFN-I innate immune pathway downstream of CLPP and may have implications for understanding myriad human diseases involving CLPP dysregulation.

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