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Tian-Sheng He, Tian Chen, Dan-Dan Wang, Liang-Guo Xu
Mitochondrial anti‑viral signaling protein (VISA), additionally termed MAVS, IPS‑1 and Cardif, is located at the outer membrane of mitochondria and is an essential adaptor in the Rig‑like receptor (RLRs) signaling pathway. Upon viral infection, activated RLRs interact with VISA on mitochondria, forming a RLR‑VISA platform, leading to the recruitment of different TRAF family members, including TRAF3, TRAF2 and TRAF6. This results in the phosphorylation and nuclear translocation of interferon regulatory factors 3 and 7 (IRF3/IRF7) by TANK binding kinase 1 (TBK1) and/or IKKε, as well as activation of NF‑κB, to induce type I interferons (IFNs) and pro‑inflammatory cytokines...
June 15, 2018: Molecular Medicine Reports
Maria Pujantell, Sandra Franco, Iván Galván-Femenía, Roger Badia, Marc Castellví, Edurne Garcia-Vidal, Bonaventura Clotet, Rafael de Cid, Cristina Tural, Miguel A Martínez, Eva Riveira-Muñoz, José A Esté, Ester Ballana
The hepatitis C virus (HCV) is a globally prevalent infectious pathogen. As many as 80% of people infected with HCV do not control the virus and develop a chronic infection. Response to interferon (IFN) therapy is widely variable in chronic HCV infected patients, suggesting that HCV has evolved mechanisms to suppress and evade innate immunity responsible for its control and elimination. Adenosine deaminase acting on RNA 1 (ADAR1) is a relevant factor in the regulation of the innate immune response. The loss of ADAR1 RNA-editing activity and the resulting loss of inosine bases in RNA are critical in producing aberrant RLR-mediated innate immune response, mediated by RNA sensors MDA5 and RIG-I...
June 12, 2018: Antiviral Research
Anu S Helin, Michelle Wille, Clara Atterby, Josef Järhult, Jonas Waldenström, Joanne R Chapman
This article provides data on primer sequences used to amplify the innate immune genes RIG-I and Mx and a set of normalizing reference genes in mallards ( Anas platyrhynchos ), and shows which reference genes are stable, per tissue, for our experimental settings. Data on the expressional changes of these two genes over a time-course of infection with low pathogenic avian influenza virus (LPAI) are provided. Individual-level data are also presented, including LPAI infection load, and per tissue gene expression of RIG-I and Mx ...
June 2018: Data in Brief
Qinya Xie, Shengwen Chen, Renyun Tian, Xiang Huang, Rilin Deng, Binbin Xue, Yuwen Qin, Yan Xu, Jingjing Wang, Mengmeng Guo, Jinwen Chen, Songqing Tang, Guangdi Li, Haizhen Zhu
Emerging evidence indicates that long non-coding RNAs (lncRNAs) regulate various biological processes, especially innate and adaptive immunity. However, the relationship between lncRNAs and interferon (IFN) pathway remains largely unknown. Here, we report that lncRNA ITPRIP-1 (lncITPRIP-1) is involved in viral infection and plays a crucial role in virus-triggered IFN signaling pathway through targeting MDA5. LncITPRIP-1 can be induced by viral infection, which is not entirely dependent on IFN signal. Besides, there is no coding potential found in lncITPRIP-1 transcript...
June 13, 2018: Journal of Virology
Hong-Yan Guo, Xing-Cui Zhang, Ren-Yong Jia
Flaviviridae family is a class of single-stranded RNA virus, which is fatal to human and animals and mainly prevalent in subtropic and tropic countries. Even though people and animals are barraged with flavivirus infection every year, we have not invented either vaccines or antiviral for most flavivirus infections yet. Innate immunity is the first line of defense in resisting pathogen invasion, serving an important role in a resisting virus. Toll-like receptors (TLRs) and retinoic acid-inducible gene I- (RIG-I-) like receptors (RLRs) are crucial pattern recognition receptors (PRRs) that play essential roles in recognizing and clearing pathogens, including resisting flavivirus...
2018: Journal of Immunology Research
Aran Singanayagam, Nicholas Glanville, Jason L Girkin, Yee Man Ching, Andrea Marcellini, James D Porter, Marie Toussaint, Ross P Walton, Lydia J Finney, Julia Aniscenko, Jie Zhu, Maria-Belen Trujillo-Torralbo, Maria Adelaide Calderazzo, Chris Grainge, Su-Ling Loo, Punnam Chander Veerati, Prabuddha S Pathinayake, Kristy S Nichol, Andrew T Reid, Phillip L James, Roberto Solari, Peter A B Wark, Darryl A Knight, Miriam F Moffatt, William O Cookson, Michael R Edwards, Patrick Mallia, Nathan W Bartlett, Sebastian L Johnston
Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations...
June 8, 2018: Nature Communications
Deepti Parashar, Mandar S Paingankar, Ashwini More, Poonam Patil, Sarika Amdekar
Chikungunya virus (CHIKV) infection can cause severe arthralgia and chronic arthritis in humans. MicroRNAs (miRNA) have demonstrated their potential use as biomarker in variety of human pathologies and infections. This study was conducted to understand the miRNA signature in early CHIKV infection stages. In the current study, we used TaqMan-based quantitative PCR method to identify the miRNA signature of host response upon CHIKV infection in human and mouse fibroblast cells. The GO enrichment analysis suggests that the putative target genes of these differentially expressed miRNAs are to be involved in RIG-I pathway, TGF-beta-signaling pathway, JAK-STAT-signaling pathway, MAPK-signaling pathway, cytokine-cytokine receptor interactions, and Fc gamma R-mediated phagocytosis...
June 5, 2018: Virus Genes
Cheryl M T Dvorak, Sumathy Puvanendiran, Michael P Murtaugh
Porcine circovirus-associated disease (PCVAD), caused by porcine circovirus 2 (PCV2), is characterized by a highly variable pathogenesis, that is manifested by various disease syndromes and includes immune evasion. Hence, even though PCVAD is effectively controlled by vaccination, pigs and farms remain infected so that continued vaccination is necessary to control disease. We investigated the molecular interactions of PCV2 and its permissive VR1BL host cell for gene expression signatures that could provide insight into mechanisms leading towards disease...
June 1, 2018: Virus Research
Devin G Fisher, Gaia M Coppock, Carolina B López
Adjuvants potentiate and direct the type of immunity elicited during vaccination. However, there is a shortage of adjuvants that elicit robust type-1 immunity required for the control of intracellular pathogens, including viruses. RNA derived from Sendai virus defective viral genomes (DVGs) stimulates RIG-I-like receptor signaling leading to type-1 immunity during infection. Here, we investigated whether a 268nt DVG-derived oligonucleotide (DDO) functions as a strong type-1 immunity-inducing adjuvant during vaccination against influenza virus...
May 31, 2018: Vaccine
Sophia Davidson, Annemarie Steiner, Cassandra R Harapas, Seth L Masters
PURPOSE OF REVIEW: Type I interferons (IFNαβ) induce the expression of hundreds of genes; thus, it is unsurprising that the initiation, transmission, and resolution of the IFNαβ-mediated immune response is tightly controlled. Mutations that alter nucleic acid processing and recognition, ablate IFNαβ-specific negative feedback mechanisms, or result in dysfunction of the proteasome system can all induce pathogenic IFNαβ signalling and are the focus of this review. RECENT FINDINGS: Recent advances have delineated the precise cytoplasmic mechanisms that facilitate self-DNA to be recognised by cGAS and self-RNA to be recognised by RIG-I or MDA-5...
May 30, 2018: Current Rheumatology Reports
Soham Gupta, Päivi Ylä-Anttila, Maria G Masucci
Upon infection, viral nucleic acids are recognized by germline-encoded pattern-recognition receptors (PRRs), and cytosolic retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) that initiate signaling pathways resulting in the production of type I IFN and pro-inflammatory cytokines. Binding of RIG-I to viral nucleic acids triggers the formation of the RIG-I signalosome where RIG-I is ubiquitinated by the TRIM25 ligase and, with the help of 14-3-3 scaffolds, further translocated to mitochondrial anti-viral signalling proteins (MAVS)...
April 11, 2018: Microbial Cell
Shu Wu, Jinpiao Lin, Ya Fu, Qishui Ou
BACKGROUND: IFN-α is widely used for the treatment of chronic hepatitis B (CHB) infection due to its high HBsAg loss. However, IFN-α treatment has a number of side effects. Thus, identification of molecular biomarkers to predict IFN-α therapeutic effect would be useful in the clinic. In this study, we aim to study the role of RIG-I in prediction of IFN-α curative effect of CHB patients. METHODS: A total of 65 CHB patients treated with PegIFN-αweekly for 48 weeks were enrolled...
May 23, 2018: Antiviral Therapy
Shotaro Uchida, Ryo Horie, Hiroki Sato, Chieko Kai, Misako Yoneda
Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes lethal encephalitis in humans. We previously reported that the V protein, one of the three accessory proteins encoded by the P gene, is one of the key determinants of the pathogenesis of NiV in a hamster infection model. Satterfield B.A. et al. have also revealed that V protein is required for the pathogenicity of henipavirus in a ferret infection model. However, the complete functions of NiV V have not been clarified. In this study, we identified UBX domain-containing protein 1 (UBXN1), a negative regulator of RIG-I-like receptor signaling, as a host protein that interacts with NiV V...
May 16, 2018: Scientific Reports
Puxian Fang, Liurong Fang, Jie Ren, Yingying Hong, Xiaorong Liu, Yunyang Zhao, Dang Wang, Guiqing Peng, Shaobo Xiao
Porcine deltacoronavirus (PDCoV) has recently emerged as an enteric pathogen that can cause serious vomiting and diarrhea in suckling piglets. The first outbreak of PDCoV occurred in the United States in 2014 and was followed by reports of PDCoV in South Korea, China, Thailand, Lao people's Democratic Republic, and Vietnam, leading to economic losses for pig farms and posing considerable threat to the swine industry worldwide. Our previous studies have shown that PDCoV encodes three accessory proteins, NS6, NS7, and NS7a, but the functions of these proteins in viral replication, pathogenesis, and immune regulation remain unclear...
May 16, 2018: Journal of Virology
Can Chen, Wenhui Fan, Jing Li, Weinan Zheng, Shuang Zhang, Limin Yang, Di Liu, Wenjun Liu, Lei Sun
Interferon (IFN)-sensitive and replication-incompetent influenza viruses are likely to be the alternatives to inactivated and attenuated virus vaccines. Some IFN-sensitive influenza vaccine candidates with modified non-structural protein 1 (NS1) are highly attenuated in IFN-competent hosts but induce robust antiviral immune responses. However, little research has been done on the manufacturability of these IFN-sensitive vaccine viruses. Here, RIG-I-knockout 293T cells were used to package the IFN-sensitive influenza A/WSN/33 (H1N1) virus expressing the mutant NS1 R38A/K41A...
2018: Frontiers in Cellular and Infection Microbiology
Lucy Bird
No abstract text is available yet for this article.
May 14, 2018: Nature Reviews. Immunology
Zifeng Zheng, Jieyu Yang, Xuan Jiang, Yalan Liu, Xiaowei Zhang, Mei Li, Mudan Zhang, Ming Fu, Kai Hu, Hanzhong Wang, Min-Hua Luo, Peng Gong, Qinxue Hu
Tick-borne encephalitis virus (TBEV) is one of the flaviviruses that targets the CNS and causes encephalitis in humans. The mechanism of TBEV that causes CNS destruction remains unclear. It has been reported that RANTES-mediated migration of human blood monocytes and T lymphocytes is specifically induced in the brain of mice infected with TBEV, which causes ensuing neuroinflammation and may contribute to brain destruction. However, the viral components responsible for RANTES induction and the underlying mechanisms remain to be fully addressed...
May 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Mickey V Patel, Zheng Shen, Charles R Wira
Despite its anatomical location, the ovary is a site of pathogen exposure in the human female reproductive tract (FRT). However, the role of ovarian stromal fibroblasts in immune protection is unclear. We generated a population of ovarian stromal fibroblasts derived from normal human ovaries that expressed the pattern recognition receptors TLR3, TLR4, RIG-I, & MDA5. Poly (I:C) and LPS, respective mimics of viral and bacterial infections, selectively upregulated antiviral gene expression and secretion of chemokines and antimicrobials...
May 9, 2018: Journal of Reproductive Immunology
Ahmed Outlioua, Marie Pourcelot, Damien Arnoult
After a viral infection and the stimulation of some pattern-recognition receptors as the toll-like receptor 3 in the endosomes or the RIG-I-like receptors in the cytosol, activation of the IKK-related kinase TBK1 leads to the production of type I interferons (IFNs) after phosphorylation of the transcription factors IRF3 and IRF7. Recent findings indicate an involvement of K63-linked polyubiquitination and of the Golgi-localized protein optineurin (OPTN) in the activation of this crucial kinase involved in innate antiviral immunity...
2018: Frontiers in Immunology
Wen Dang, Lei Xu, Yuebang Yin, Sunrui Chen, Wenshi Wang, Mohamad S Hakim, Kyeong-Ok Chang, Maikel P Peppelenbosch, Qiuwei Pan
Norovirus represents the main cause of acute nonbacterial gastroenteritis worldwide. In immunocompromised patients, it bears high risk of causing chronic infection with significant morbidity and mortality. The lack of specific treatment prompts the development of anti-norovirus agents. In this study, we have investigated the role of interferon (IFN) response and evaluated antiviral activities of different IFNs against human norovirus (HuNoV) replication using a HuNoV replicon model. We found that HuNoV RNA replication was sensitive to all types of IFNs, including IFNα (type I), IFNγ (type II), IFNλ1 and 3 (type III)...
May 10, 2018: Antiviral Research
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