scholarly journals Activation and Evasion of RLR Signaling by DNA Virus Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Junli Jia ◽  
Jiangan Fu ◽  
Huamin Tang
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Viral Infections ◽  
Infection Process ◽  
Research Progress ◽  
Ligand Recognition ◽  
Dna Virus ◽  
Antiviral Immune Response ◽  
Host Immune Responses ◽  
Inducible Gene

Antiviral innate immune response triggered by nucleic acid recognition plays an extremely important role in controlling viral infections. The initiation of antiviral immune response against RNA viruses through ligand recognition of retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) was extensively studied. RLR’s role in DNA virus infection, which is less known, is increasing attention. Here, we review the research progress of the ligand recognition of RLRs during the DNA virus infection process and the viral evasion mechanism from host immune responses.

scholarly journals Phosphatase Cdc25A Negatively Regulates the Antiviral Immune Response by Inhibiting TBK1 Activity

2018 ◽  
Vol 92 (19) ◽  
Author(s):  
Dandan Qi ◽  
Lei Hu ◽  
Tong Jiao ◽  
Tinghong Zhang ◽  
Xiaomei Tong ◽  
...  
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Phosphatase Activity ◽  
Signaling Pathway ◽  
Sendai Virus ◽  
Rna Virus ◽  
Negative Regulator ◽  
Luciferase Assay ◽  
Dna Virus ◽  
Antiviral Immune Response

ABSTRACT The phosphatase Cdc25A plays an important role in cell cycle regulation by dephosphorylating its substrates, such as cyclin-dependent kinases. In this study, we demonstrate that Cdc25A negatively regulates RIG-I-mediated antiviral signaling. We found that ectopic expression of Cdc25A in 293T cells inhibits the activation of beta interferon (IFN-β) induced by Sendai virus and poly(I·C), while knockdown of Cdc25A enhances the transcription of IFN-β stimulated by RNA virus infection. The inhibitory effect of Cdc25A on the antiviral immune response is mainly dependent on its phosphatase activity. Data from a luciferase assay indicated that Cdc25A can inhibit TBK1-mediated activation of IFN-β. Further analysis indicated that Cdc25A can interact with TBK1 and reduce the phosphorylation of TBK1 at S172, which in turn decreases the phosphorylation of its downstream substrate IRF3. Consistently, knockdown of Cdc25A upregulates the phosphorylation of both TBK1-S172 and IRF3 in Sendai virus-infected or TBK1-transfected 293T cells. In addition, we confirmed that Cdc25A can directly dephosphorylate TBK1-S172-p. These results demonstrate that Cdc25A inhibits the antiviral immune response by reducing the active form of TBK1. Using herpes simplex virus 1 (HSV-1) infection, an IFN-β reporter assay, and reverse transcription-quantitative PCR (RT-qPCR), we demonstrated that Cdc25A can also inhibit DNA virus-induced activation of IFN-β. Using a vesicular stomatitis virus (VSV) infection assay, we confirmed that Cdc25A can repress the RIG-I-like receptor (RLR)-mediated antiviral immune response and influence the antiviral status of cells. In conclusion, we demonstrate that Cdc25A negatively regulates the antiviral immune response by inhibiting TBK1 activity. IMPORTANCE The RLR-mediated antiviral immune response is critical for host defense against RNA virus infection. However, the detailed mechanism for balancing the RLR signaling pathway in host cells is not well understood. We found that the phosphatase Cdc25A negatively regulates the RNA virus-induced innate immune response. Our studies indicate that Cdc25A inhibits the RLR signaling pathway via its phosphatase activity. We demonstrated that Cdc25A reduces TBK1 activity and consequently restrains the activation of IFN-β transcription as well as the antiviral status of nearby cells. We showed that Cdc25A can also inhibit DNA virus-induced activation of IFN-β. Taken together, our findings uncover a novel function and mechanism for Cdc25A in regulating antiviral immune signaling. These findings reveal Cdc25A as an important negative regulator of antiviral immunity and demonstrate its role in maintaining host cell homeostasis following viral infection.

scholarly journals Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections

2021 ◽  
Author(s):  
Karthick Dharmalingam ◽  
Amandeep Birdi ◽  
Sojit Tomo ◽  
Karli Sreenivasulu ◽  
Jaykaran Charan ◽  
...  
Keyword(s):  
Immune Response ◽  
Trace Elements ◽  
Viral Entry ◽  
Viral Infections ◽  
Inhibitory Effect ◽  
Antioxidants Activity ◽  
Host Immune Responses ◽  
Complex Interactions ◽  
Downstream Processes

AbstractNutritional deficiency is associated with impaired immunity and increased susceptibility to infections. The complex interactions of trace elements with the macromolecules trigger the effective immune response against the viral diseases. The outcome of various viral infections along with susceptibility is affected by trace elements such as zinc, selenium, iron, copper, etc. due to their immuno-modulatory effects. Available electronic databases have been comprehensively searched for articles published with full text available and with the key words “Trace elements”, “COVID-19”, “Viral Infections” and “Immune Response” (i.e. separately Zn, Se, Fe, Cu, Mn, Mo, Cr, Li, Ni, Co) appearing in the title and abstract. On the basis of available articles we have explored the role of trace elements in viral infections with special reference to COVID-19 and their interactions with the immune system. Zinc, selenium and other trace elements are vital to triggerTH1 cells and cytokine-mediated immune response for substantial production of proinflammatory cytokines. The antiviral activity of some trace elements is attributed to their inhibitory effect on viral entry, replication and other downstream processes. Trace elements having antioxidants activity not only regulate host immune responses, but also modify the viral genome. Adequate dietary intake of trace elements is essential for activation, development, differentiation and numerous functions.

scholarly journals Dendritic Cell Precursors Are Permissive to Dengue Virus and Human Immunodeficiency Virus Infection

2005 ◽  
Vol 79 (12) ◽  
pp. 7291-7299 ◽  
Author(s):  
Wing-Hong Kwan ◽  
Anna-Marija Helt ◽  
Concepción Marañón ◽  
Jean-Baptiste Barbaroux ◽  
Anne Hosmalin ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Dengue Virus ◽  
Blood Monocytes ◽  
Dengue Virus Infection ◽  
Differentiation Potential ◽  
Antiviral Immune Response ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT CD14+ interstitial cells reside beneath the epidermis of skin and mucosal tissue and may therefore play an important role in viral infections and the shaping of an antiviral immune response. However, in contrast to dendritic cells (DC) or blood monocytes, these antigen-presenting cells (APC) have not been well studied. We have previously described long-lived CD14+ cells generated from CD34+ hematopoietic progenitors, which may represent model cells for interstitial CD14+ APC. Here, we show that these cells carry DC-SIGN and differentiate into immature DC in the presence of granulocyte-macrophage colony-stimulating factor. We have compared the CD14+ cells and the DC derived from these cells with respect to dengue virus and human immunodeficiency virus type 1 (HIV-1) infection. Both cell types are permissive to dengue virus infection, but the CD14+ cells secrete the anti-inflammatory cytokine interleukin 10 and no tumor necrosis factor alpha. Regarding HIV, the CD14+ cells are permissive to HIV-1, release higher p24 levels than the derived DC, and more efficiently activate HIV Pol-specific CD8+ memory T cells. The CD14+ DC precursors infected with either virus retain their DC differentiation potential. The results suggest that interstitial CD14+ APC may contribute to HIV-1 and dengue virus infection and the shaping of an antiviral immune response.

scholarly journals Infection, Inflammation and Immunity in Covid-19 Infection

2021 ◽  
Vol 48 (3) ◽  
pp. 77-82
Author(s):  
R. Cherneva ◽  
Z. Cherneva
Keyword(s):  
Immune Response ◽  
Virus Infection ◽  
Immune Responses ◽  
Systemic Inflammation ◽  
Multiple Organ ◽  
Host Immunity ◽  
Effective Prevention ◽  
Systemic Complications ◽  
Host Immune Responses ◽  
Prevention And Treatment

Abstract The COVID-19 pandemic caused by the SARS-CoV-2 has increased the burden on healthcare system. Despite some progress in its diagnostics has been made, effective prevention and treatment are still insufficient. Since SARS-CoV-2 infections often cause systemic inflammation and multiple organ failure, the therapeutic options aimed at modulating the host immune responses to prevent subsequent systemic complications are demanding. The review provides a summary of the SARS-CoV-2 virus infection and underlines the current perception of pulmonary host’s immune response and its contributions to disease severity and systemic inflammation. Signaling pathways which have the potential to manipulate host immunity and improve clinical outcomes are also presented.

scholarly journals Inhibition of Antiviral Innate Immunity by Avibirnavirus VP3 via Blocking TBK1-TRAF3 Complex Formation and IRF3 Activation

mSystems ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Tingjuan Deng ◽  
Boli Hu ◽  
Xingbo Wang ◽  
Lulu Lin ◽  
Jianwei Zhou ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Virus Infection ◽  
Complex Formation ◽  
Rna Virus ◽  
Critical Role ◽  
Type I ◽  
Antiviral Immune Response ◽  
Critical Residue ◽  
Irf3 Activation

ABSTRACT The host innate immune system develops various strategies to antagonize virus infection, and the pathogen subverts or evades host innate immunity for self-replication. In the present study, we discovered that Avibirnavirus infectious bursal disease virus (IBDV) VP3 protein significantly inhibits MDA5-induced beta interferon (IFN-β) expression by blocking IRF3 activation. Binding domain mapping showed that the CC1 domain of VP3 and the residue lysine-155 of tumor necrosis factor receptor-associated factor 3 (TRAF3) are essential for the interaction. Furthermore, we found that the CC1 domain was required for VP3 to downregulate MDA5-mediated IFN-β production. A ubiquitination assay showed that lysine-155 of TRAF3 was the critical residue for K33-linked polyubiquitination, which contributes to the formation of a TRAF3-TBK1 complex. Subsequently, we revealed that VP3 blocked TRAF3-TBK1 complex formation through reducing K33-linked polyubiquitination of lysine-155 on TRAF3. Taken together, our data reveal that VP3 inhibits MDA5-dependent IRF3-mediated signaling via blocking TRAF3-TBK1 complex formation, which improves our understanding of the interplay between RNA virus infection and the innate host antiviral immune response. IMPORTANCE Type I interferon plays a critical role in the host response against virus infection, including Avibirnavirus. However, many viruses have developed multiple strategies to antagonize the innate host antiviral immune response during coevolution with the host. In this study, we first identified that K33-linked polyubiquitination of lysine-155 of TRAF3 enhances the interaction with TBK1, which positively regulates the host IFN immune response. Meanwhile, we discovered that the interaction of the CC1 domain of the Avibirnavirus VP3 protein and the residue lysine-155 of TRAF3 reduced the K33-linked polyubiquitination of TRAF3 and blocked the formation of the TRAF3-TBK1 complex, which contributed to the downregulation of host IFN signaling, supporting viral replication.

scholarly journals Exogenous Interleukin-33 Contributes to Protective Immunity via Cytotoxic T-Cell Priming against Mucosal Influenza Viral Infection

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 840 ◽  
Author(s):  
Chae Won Kim ◽  
Hye Jee Yoo ◽  
Jang Hyun Park ◽  
Ji Eun Oh ◽  
Heung Kyu Lee
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
T Cell ◽  
Viral Infections ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Respiratory Illness ◽  
Cytotoxic T Cell ◽  
Antiviral Immune Response ◽  
Cytotoxic T Cell Responses

Influenza is an infectious respiratory illness caused by the influenza virus. Though vaccines against influenza exist, they have limited efficacy. To additionally develop effective treatments, there is a need to study the mechanisms of host defenses from influenza viral infections. To date, the mechanism by which interleukin (IL)-33 modulates the antiviral immune response post-influenza infection is unclear. In this study, we demonstrate that exogenous IL-33 enhanced antiviral protection against influenza virus infection. Exogenous IL-33 induced the recruitment of dendritic cells, increased the secretion of pro-inflammatory cytokine IL-12, and promoted cytotoxic T-cell responses in the local microenvironment. Thus, our findings suggest a role of exogenous IL-33 in the antiviral immune response against influenza infection.

scholarly journals The Human Papillomavirus (HPV) E1 protein regulates the expression of cellular genes involved in immune response

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Leonardo Josué Castro-Muñoz ◽  
Joaquín Manzo-Merino ◽  
J. Omar Muñoz-Bello ◽  
Leslie Olmedo-Nieva ◽  
Alberto Cedro-Tanda ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Papillomavirus ◽  
Defense Mechanisms ◽  
Viral Infections ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Antiviral Immune Response ◽  
E1 Protein ◽  
Cellular Genes ◽  
Proliferation And Differentiation

Abstract The Human Papillomavirus (HPV) E1 protein is the only viral protein with enzymatic activity. The main known function of this protein is the regulation of the viral DNA replication. Nevertheless, it has been demonstrated that the ablation of HPV18 E1 mRNA in HeLa cells promotes a deregulation of several genes, particularly those involved in host defense mechanisms against viral infections; however, the specific contribution of E1 protein in HPV-independent context has not been studied. The aim of this work was to determine the effect of the HPV E1 protein in the regulation of cellular gene expression profiles evaluated through RNA-seq. We found that E1 proteins from HPV16 and 18 induced an overexpression of different set of genes associated with proliferation and differentiation processes, as well as downregulation of immune response genes, including IFNβ1 and IFNλ1 and Interferon-stimulated gene (ISG), which are important components involved in the antiviral immune response. Together, our results indicate that HR-(High-Risk) and LR-(Low-Risk) HPV E1 proteins play an important role in inhibiting the anti-viral immune response.

scholarly journals Antiviral and Immunoregulatory Effects of Indoleamine-2,3-Dioxygenase in Hepatitis C Virus Infection

2015 ◽  
Vol 7 (5) ◽  
pp. 530-544 ◽  
Author(s):  
Quentin Lepiller ◽  
Eric Soulier ◽  
Qisheng Li ◽  
Mélanie Lambotin ◽  
Jochen Barths ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Inhibitory Effect ◽  
Hcv Infection ◽  
Antiviral Immune Response ◽  
Host Immune Responses ◽  
Indoleamine 2,3 Dioxygenase ◽  
Important Regulator ◽  
Innate Defence

In patients with hepatitis C virus (HCV) infection, enhanced activity of indoleamine-2,3-dioxygenase 1 (IDO) has been reported. IDO - a tryptophan-catabolizing enzyme - has been considered as both an innate defence mechanism and an important regulator of the immune response. The molecular mechanism of IDO induction in HCV infection and its role in the antiviral immune response remain unknown. Using primary human hepatocytes, we show that HCV infection stimulates IDO expression. IDO gene induction was transient and coincided with the expression of types I and III interferons (IFNs) and IFN-stimulated genes in HCV-infected hepatocytes. Overexpression of hepatic IDO prior to HCV infection markedly impaired HCV replication in hepatocytes, suggesting that IDO limits the spread of HCV within the liver. siRNA-mediated IDO knock-down revealed that IDO functions as an IFN-mediated anti-HCV effector. Hepatic IDO was most potently induced by IFN-γ, and ongoing HCV replication could significantly upregulate IDO expression. IRF1 (IFN-regulatory factor 1) and STAT1 (signal transducer and activator of transcription 1) regulated hepatic IDO expression. Hepatic IDO expression also had a significant inhibitory effect on CD4+ T-cell proliferation. Our data suggest that hepatic IDO plays a dual role during HCV infection by slowing down viral replication and also regulating host immune responses.

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