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Regulation of Antiviral Immunity by Mitochondrial Dynamics
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Mohsin Khan, Hasan Imam, Saiful Anam Mir
In higher organisms, viral RNA is sensed by TLRs (Toll-like receptors), RIG-I (Retinoic acid inducible gene I) and RLRs (RIG-I like receptors) (Yoneyama et al., 2004). RIG-I and RLRs contain RNA helicase domain. RIG-I contains a C-terminal regulatory domain that can sense the 5ʹ triphosphate of RNA (Yoneyama et al., 2004). Multiple RLRs detect distinct classes of RNA viruses (Zevini et al., 2017). Binding of viral RNA with RIG-I and RLRs induces conformational changes and facilitate their interaction with MAVS (Seth et al., 2005). MAVS then activates cytosolic kinase TBK1 followed by IRF3 activation. Activated IRF3 translocates into the nucleus and activate type I interferon production and also other inflammatory molecules (Seth et al., 2005; Zevini et al., 2017).
Hepatitis E Virus
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Kavita Lole, Prudhvi Lal Bhukya, Bangari Haldipur
This domain has poly ADP-ribose binding activity,57,58 but its significance in HEV biology is not clear. Nan et al. showed that macro domain blocks the phosphorylation activity of IRF3 and further inhibits the action type 1 IFN induction.59 It also interacts with the light-chain subunit of human ferritin to inhibit ferritin secretion.60
Viral-Induced Asthma and Chronic Obstructive Pulmonary Disease
Published in Sunit K. Singh, Human Respiratory Viral Infections, 2014
It is increasingly realized that viral and bacterial coinfection could be an important causative factor in exacerbations. Interaction between influenza and bacterial infection is known to promote the development of pneumonia40 and patients with asthma have a known risk of developing invasive pneumonia. Further, individuals with COPD co-infected with RV and Haemophilus influenzae have exhibited increased severity of exacerbations compared to those without coinfection.41,42 Johnston and colleagues recently demonstrated that experimental inoculation–infection with RV in COPD was followed by secondary bacterial infection in more than half of the inoculated patients.43 Thus, both influenza and RV infection may impede bacterial host defense mechanisms and increase the risk of exacerbations as well as secondary pneumonia. The potential importance of coinfection is reflected by increasing number of research approaches in the field with revelation of intriguing molecular mechanisms and clinical observations. For example, experimental data have identified a potential role of the transcription factor IRF3 in reduced antibacterial defense evoked by viral infection. Thus, inducement of IRF3 by dsRNA, produced by viral infection and acting on cytoplasmic RIG-I-like receptors, reduced toll-like receptor (TLR)-mediated antibacterial defense by the suppression of the expression of IL-12 and IL-23.44 This finding increases the interest in the pharmacology of IRF3 inhibition.45
Evaluation of the Effects of Nobiletin on Toll-Like Receptor 3 Signaling Pathways in Prostate Cancer In Vitro
Published in Nutrition and Cancer, 2021
Asuman Deveci Ozkan, Mehmet Sarihan, Suleyman Kaleli
Toll-like receptors (TLRs) are well-protected pattern recognition receptors (PRRs) that are expressed in human epithelial and immune cells as well as tumor cells and play crucial roles in tumorigenesis, development and metastasis (1). The TLR family is expressed and identified as 10 different (TLR1-10) receptors in humans (2). The receptors in the TLR family recognize conserved microbial structures called pathogen-associated molecular patterns (PAMPs) (3). The localization of specialized TLRs to recognize PAMPs differs within the cell (4). TLR3 as an endosomal PRR recognizes intracellular viral dsRNA (1). Stimulation of TLR3 with its ligand (polyinosinic-polycytidilic acid, Poly I:C), initiates two different pathways. Firstly, TLR3 selectively activates interferon regulatory factor 3 (IRF3). After activation of IRF3, it translocates into the nucleus and initiates the expression of the inflammatory cytokines as well as type I interferons (5–11). Secondly, stimulating TLR3 by Poly I:C initiates the TRIF/RIPK1/FADD pathway which is resulted in NLRP3 inflammasome activation through CASP8 activity and also can trigger CASP8-dependent apoptosis (6,11–13).
Double-edged effects of interferons on the regulation of cancer-immunity cycle
Published in OncoImmunology, 2021
Xiao Zhang, Song Wang, Yuanyuan Zhu, Minghui Zhang, Yan Zhao, Zhengbin Yan, Qiuxu Wang, Xiaobo Li
Both IFN-α and IFN-β regulate intrinsic and extrinsic apoptotic pathways.99,100 Mechanistically, IFN-α and IFN-β induce the transcription of the TP53 gene, inhibit proliferation, and induce apoptosis of cancer cells.101 Moreover, they also directly induce the production of pro-apoptotic factors, such as TRAIL and FAS102,103 and enhance their pro-apoptotic effects in various malignant cell types.104,105 Additionally, IRF family members are well-known ISGs induced by type I IFNs.25 Most members of the IRF family, such as IRF1, IRF3, and IRF5, have been documented to induce cell death in various malignant tumor types.106–108 Although the pro-cytotoxic effects of type III and other members of type I IFNs are currently not well studied, considering that the ISGs induced by them are almost same, it is reasonable to deduce that most members of type I and type III IFNs could directly induce malignant cell death. As expected, several recent studies have shown that type III IFNs, such as IFN-λ1, IFN-λ2, and IFN-λ4, induce cell death in various malignant tumor types.90,109–112
Toll-like receptors: Significance, ligands, signaling pathways, and functions in mammals
Published in International Reviews of Immunology, 2018
Mallenahally Kusha Vidya, V. Girish Kumar, Veerasamy Sejian, Madiajagan Bagath, Govindan Krishnan, Raghavendra Bhatta
TRIF molecule interacts with TRAF-6 and recruits receptor-interacting protein 1 (RIP-1) which is ubiquitinated by IKKi /TBK1. RIP-1 activates TAK-I complex, which is followed by activation of NF-κB and MAPK.5 Contrarily, TRAF-3 recruits TBK1 and IKKi, which cause IRF3 phosphorylation.36 IRF3 forms a dimer and is translocated into the nucleus. Pellino 1 binds to DEAF-1 and influences binding of IRF3 to IFNβ promoter. Thus IRF3 induces the expression of type I IFN genes.38