Innate Antiviral Immunity
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Innate Antiviral Immunity
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Author : Karen Mossman
language : en
Publisher: Humana
Release Date : 2018-08-03
Innate Antiviral Immunity written by Karen Mossman and has been published by Humana this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-08-03 with Medical categories.
This book explores methods to study the complex and evolving interplay between a virus and its host that range from model systems to the detection of chemical molecules. The collection starts with the application of humanized mice and zebrafish as model organisms to study virus-host interactions and induction of innate immune responses. Subsequent chapters outline diverse methods to detect small interfering RNAs, microRNAs, and virus-derived dsRNA from a variety of cells, tissues, and organisms, as well as to interrogating the cytosolic RNA and DNA sensing pathways, including using RNA PAMPs as molecular tools, purification of cGAMP from virus particles and infected cells, and mechanisms to visualize the subcellular localization and activation of the adaptor proteins MAVS and STING. Cutting-edge methods, including high-throughput and genome-wide CRISPR/Cas9 screens, chromosome conformation capture, and whole-exome sequencing, are described to identify novel mediators, pathways, and variants underlying host susceptibility. Given the importance of studying these pathways and players under physiologic conditions, methods describing the isolation of primary mouse sensory neurons and group 2 innate lymphoid cells are also provided. Finally, this collection comes full circle back to the whole organism level and concludes with epidemiological methods to investigate virus-host interactions and the induction of innate immunity. Written for the Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Innate Antiviral Immunity: Methods and Protocols spans a diverse array of approaches to study and elucidate the intricacies of this vital area of study. The chapter 'Morphological Separation of Clustered Nuclei in Histological Images' is published open access under a CC BY 4.0 license at link.springer.com.
Control Of Innate Antiviral Immunity By Hiv 1
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Author : Arjun Rustagi
language : en
Publisher:
Release Date : 2013
Control Of Innate Antiviral Immunity By Hiv 1 written by Arjun Rustagi and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with categories.
Human immunodeficiency virus 1 (HIV-1) infection continues to be a major public health problem, with 34 million people infected worldwide. Cell-intrinsic innate immune defenses are essential for the control of HIV-1 infection but are subverted by the virus to establish successful infection. Interferon regulatory factor 3 (IRF3) is a central transcription factor of innate immune signaling that is activated by cellular pattern recognition receptors in response to the presence of non-self molecules (e.g. viral RNA or DNA). Activation of IRF3 induces the expression of antiviral and immunomodulatory genes whose products can suppress HIV-1 infection within target cells and regulate the adaptive immune response to infection. We have found that during acute infection HIV-1 evades innate antiviral immunity through the actions of HIV-1 viral protein u (Vpu), which interacts with IRF3 and inhibits its activity. While HIV infection eventually results in proteolytic destruction of IRF3 at later time points of acute infection, we found that inhibition of IRF3-dependent IFN-[Beta] transcription by Vpu occurs at early time points. In addition, Vpu blocked both IRF3- and NF[kappa]B-dependent activities at the IFN-[Beta] promoter. These findings led us to hypothesize that Vpu blocks IRF3 activation to prevent IRF3 from carrying out the necessary biochemical steps to drive antiviral gene expression. We investigated the process of Vpu regulation of IRF3, and found that IRF3 and Vpu form a stable complex during infection of CD4+ T cells with HIV-1. Using truncation and deletion mutants of recombinant IRF3, we mapped the binding epitope for Vpu on IRF3 to a region of IRF3 protein called the IRF association domain. This domain is the site necessary for homodimerization of IRF3 molecules after activation and interaction with transcriptional cofactors. Thus, we hypothesized that Vpu alters IRF3 dimerization and cofactor interaction. Indeed, when we examined the IRF3 activation pathway in the presence of Vpu to identify the site of the Vpu-induced block in IRF3 activity, we found that Vpu inhibited IRF3 dimerization and CBP binding. We predict that Vpu antagonism of IRF3-directed innate immunity is a key step in HIV-1 pathogenesis during acute infection. Further, IRF3 depletion and control of innate antiviral immunity by HIV-1 may correlate with disease progression in HIV-infected patients. To test these predictions, we have developed two novel monoclonal antibodies to human IRF3 to support the study of IRF3 activation and HIV-mediated IRF3 depletion among patient samples in a high-throughput manner. One of these antibodies, AR-1, is specific for activated IRF3. The other, AR-2, detects total IRF3 levels in a flow cytometric assay of blood leukocytes. Use of these new antibodies to study IRF-3 levels during HIV infection could reveal an innate immune correlate of HIV-1 disease progression, while studies to fully define the interaction between Vpu and IRF3 may reveal novel targets for the development of drugs that preserve IRF3 activity during HIV-1 infection.
Community Series In Antiviral Innate Immune Sensing Regulation And Viral Immune Evasion Volume Ii
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Author : Chenhe Su
language : en
Publisher: Frontiers Media SA
Release Date : 2024-01-18
Community Series In Antiviral Innate Immune Sensing Regulation And Viral Immune Evasion Volume Ii written by Chenhe Su and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2024-01-18 with Medical categories.
This Research Topic is the second volume of the “Community Series in Antiviral Innate Immune Sensing, Regulation, and Viral Immune Evasion”. Please see the first volume here. The innate immune system is crucial to defend against viruses or other pathogenic microbes in the early phases of infection. The response starts with detecting evolutionarily conserved structures, termed pathogen-associated molecular patterns (PAMPs), by a set of germline-encoded pattern-recognition receptors (PRRs). Following the detection of specific viral PAMPs, PRRs trigger the activation of intracellular signaling cascades, ultimately leading to the induction of type I interferons (IFNs), pro-inflammatory cytokines, and antiviral genes through the activation of interferon regulatory factor 3 (IRF3) and IRF7. Antiviral pathways need to be tightly regulated to ensure successful antiviral defenses and avoid aberrant or dysregulation of host immune signaling. We believe that the Research Topic will give updated insights into the dynamic fields of PAMPs sensing in antiviral innate immunity and viral immune evasion. We hope it will serve the purpose of encouraging new research. This Research Topic will provide an overall picture of antiviral innate immune sensing signal pathways, regulation, and viral immune evasion. We welcome the submission of Original Research, Review, Mini-Review, Hypothesis and Theory, and Perspective articles that cover, but are not limited to, the following subtopics:
Sensing Dna In Antiviral Innate Immunity
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Author : Chunfu Zheng
language : en
Publisher: Frontiers Media SA
Release Date : 2021-09-08
Sensing Dna In Antiviral Innate Immunity written by Chunfu Zheng and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-09-08 with Medical categories.
The Viral Evasion Of Antiviral Innate Immunity
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Author : Chunfu Zheng
language : en
Publisher: Frontiers Media SA
Release Date : 2022-11-01
The Viral Evasion Of Antiviral Innate Immunity written by Chunfu Zheng and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-11-01 with Science categories.
Nucleic Acid Sensors And Antiviral Immunity
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Author : Dr. Prakash Sambhara
language : en
Publisher: CRC Press
Release Date : 2012-11-26
Nucleic Acid Sensors And Antiviral Immunity written by Dr. Prakash Sambhara and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-11-26 with Science categories.
The discovery of Toll-like receptors (TLRs) in the late 1990s ushered in a new age of discovery for innate immunity. The importance of TLRs for immunology and biomedical research was recognized with the Nobel Prize for Medicine or Physiology in 2011. The prize was shared by three scientists: Ralph Steinman (for the discovery of dendritic cells, whi
Porcine Innate Antiviral Immunity
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Author :
language : en
Publisher:
Release Date : 2008
Porcine Innate Antiviral Immunity written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with categories.
The immediate antiviral defense residing in the innate immune system of multicellular organisms critically determines the outcome of viral infection. This dissertation presents a study of the "effectors" and "receptors" of porcine innate immunity in infection caused by porcine reproductive and respiratory syndrome virus (PRRSV), which is the most devastating pathogen impacting the swine industry. In the first investigation, eleven novel porcine host defense peptides (HDPs), [Beta]-defensins (pBDs), were identified and characterized. All of these peptides have a consensus [Beta]-defensin motif and phylogenetically are similar to orthologs from other species. A differential expression pattern for these 11 newly identified genes was found. For example, pBD-2 and pBD-3 were expressed in bone marrow, lung, skin and other lymphoid tissues. pBD-2 and pBD-3 were further characterized for their gene structure, and antimicrobial activity of synthetic peptides. The second study was conducted to evaluate PRRSV-induced differential expression of porcine HDPs and direct antiviral activity of selected HDPs against PRRSV. In vitro incubation of PRRSV with synthetic pBD-3 or protegrin-4 (PG-4) significantly inhibited viral infectivity. Using nine protegrin-derived peptides, it was determined that cyclization of PG-4 increased anti-PRRSV activity and mutation of some residues in PG-4 diminished some of the activity. These findings suggest the potential role of porcine HDPs as a group of innate antiviral effectors. In the third and fourth investigations, porcine Toll-like receptor (TLR) 3 and TLR7 were identified and functionally expressed. Increased expression of TLR3 was observed in PRRSV-infected porcine lungs. Stimulation of porcine alovelar macrophages with poly (I:C), a synthetic TLR3 ligand, increased expression of interferon-[Beta], and suppressed PRRSV infectivity. Activation of porcine TLR3 overexpressed in a PRRSV-sensitive cell line, elicited antiviral responses to PRRSV infection. Partial silencing of TLR3 in PAMs resulted in increased PRRSV infection. In summary, these data provide molecular information on porcine TLR3 and TLR7, and their involvement in PRRSV pathogenesis, which may elicit new strategies to prevent this costly swine disease.
Nucleic Acid Sensors And Antiviral Immunity
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Author : Dr. Prakash Sambhara
language : en
Publisher: CRC Press
Release Date : 2012-11-26
Nucleic Acid Sensors And Antiviral Immunity written by Dr. Prakash Sambhara and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-11-26 with Medical categories.
The discovery of Toll-like receptors (TLRs) in the late 1990s ushered in a new age of discovery for innate immunity. The importance of TLRs for immunology and biomedical research was recognized with the Nobel Prize for Medicine or Physiology in 2011. The prize was shared by three scientists: Ralph Steinman (for the discovery of dendritic cells, which express TLRs and whose activation by them provides a link between innate and adaptive immunity), Jules Hoffman (who made the pioneering observation of Toll in fruit fly anti-fungal immunity) and Bruce Beutler (who uncovered the role of TLR4 in the response to LPS). Work on TLRs inspired many researchers, and led to a search for other receptors in innate immunity. There are now several additional families of such receptors known, notably RIG-I-like receptors (RLRs), C-type lectin receptors (CLRs) and AIM2-like receptors (ALRs). A notable feature is the detection of nucleic acids from pathogens, but also from host cells in certain contexts, particularly in autoimmune diseases. Nucleic Acid Sensors and Antiviral Immunity presents a timely and extensive account of the detection of nucleic acids in infection and inflammation. We have chapters by Beutler, Hoffman and Shizuo Akira, who is the most cited immunologist of the past ten years, for his work on innate immunity, which gives us an indication of the importance of the field. Several other pioneers in the field present comprehensive and highly lucid up-to-date accounts of their particular interests, revealing the large amount of activity in the past few years, as the literature continues to grow and become ever more complex. The fly yet again provides new insights, and anti-viral mechanisms in this key model organism are described. Other topics include the ability of viruses such as poxviruses, hepatitis C virus and HIV to interfere with detection and signalling; new insights into signalling including subcellular localization of signalling proteins, complex regulation of TLRs and RLRs by ubiquination and negative regulation by miRNAs; and the role of autophagy in antiviral defence. The importance of the RLRs in viral detection is widely reviewed. DNA sensing by ALRs and other receptors is extensively described, and the prospect of additional as yet unknown receptors for DNA debated, revealing a field that is still burgeoning. The prospect of therapeutic utility is covered in the context of using nucleic acids or other compounds as agents to promote anti-viral immunity. This book therefore represents an unprecedented account of this important aspect of immunology, by a stellar cast of authors who have defined the field. We have a key resource which should act as a primary source of information. The chapters will inspire researchers to continue on their quest to provide mechanistic insights into anti-viral innate immunity. The discoveries provide us with new strategies in the never ending war between humanity and viral infection, and will help in the ultimate goal to provide treatments to use against viruses which continue to present a major threat to human health.
Role Of Deacetylation In Innate Antiviral Immunity
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Author : Inna Nusinzon
language : en
Publisher:
Release Date : 2006
Role Of Deacetylation In Innate Antiviral Immunity written by Inna Nusinzon and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006 with categories.
Autophagy
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Author : Steve S.-L. Chen
language : en
Publisher: Elsevier Inc. Chapters
Release Date : 2013-09-03
Autophagy written by Steve S.-L. Chen and has been published by Elsevier Inc. Chapters this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-09-03 with Medical categories.
Autophagy, a conserved “self-eating” process aimed at maintaining cellular homeostasis, has diverse functions in host–pathogen interactions. Many viruses, including hepatitis C virus (HCV), have evolved strategies to subvert the host autophagic machinery and enhance their own replication. Nevertheless, the underlying mechanism for the role of autophagy in HCV replication and whether autophagy modulates the innate immunity in HCV infection are still poorly understood. In a recent study, we showed that infection of hepatoma Huh7 cells with cell culture-derived HCVcc perturbs the autophagy pathway, which proceeds to fusion of the autophagosome with a lysosome, through the unfolded protein response (UPR), to promote HCV RNA replication. Deregulation of the UPR and autophagy by gene silencing or interference with complete autolysosome formation with inhibitors such as chloroquine and Bafilomycin A1 impeded HCV RNA replication. Interruption of the UPR and autophagy concurred with upregulation of the HCV pathogen-associated molecular pattern (PAMP) RNA-mediated cytoplasmic retinoic acid-inducible gene-I signaling and interferon beta (IFN-β)-mediated antiviral responses. With the battery of UPR and autophagy inducers, we demonstrated that activated UPR–autophagy signaling downregulates HCV PAMP RNA-mediated innate immunity even in a context without HCV infection. Moreover, disruption of the autophagic flux by chloroquine or individual knockdown of lysosome-associated membrane protein 2 and RAS-related GTP-binding protein 7, which are critical for fusion of autophagosomes with lysosomes, mitigated UPR- and autophagy-mediated suppression of innate antiviral immunity. Our results manifest that the UPR and autophagy machinery acts as a negative regulator in innate immunity, thus stimulating HCV replication. Our study will also benefit the development of efficacious anti-HCV therapeutic and intervention approaches targeting and/or modifying the UPR and autophagy signaling pathway.
