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https://www.readbyqxmd.com/read/29925692/double-stranded-rna-innate-immune-response-activation-from-long-term-adeno-associated-virus-vector-transduction
#1
Wenwei Shao, Lauriel F Earley, Zheng Chai, Xiaojing Chen, Junjiang Sun, Ting He, Meng Deng, Matthew L Hirsch, Jenny Ting, R Jude Samulski, Chengwen Li
Data from clinical trials for hemophilia B using adeno-associated virus (AAV) vectors have demonstrated decreased transgenic coagulation factor IX (hFIX) expression 6-10 weeks after administration of a high vector dose. While it is likely that capsid-specific cytotoxic T lymphocytes eliminate vector-transduced hepatocytes, thereby resulting in decreased hFIX, this observation is not intuitively consistent with restored hFIX levels following prednisone application. Although the innate immune response is immediately activated following AAV vector infection via TLR pathways, no studies exist regarding the role of the innate immune response at later time points after AAV vector transduction...
June 21, 2018: JCI Insight
https://www.readbyqxmd.com/read/29906476/adar1-affects-hcv-infection-by-modulating-innate-immune-response
#2
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
https://www.readbyqxmd.com/read/29899107/lncitprip-1-positively-regulates-innate-immune-response-through-promoting-oligomerization-and-activation-of-mda5
#3
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
https://www.readbyqxmd.com/read/29880757/comparison-of-porcine-airway-and-intestinal-epithelial-cell-lines-for-the-susceptibility-and-expression-of-pattern-recognition-receptors-upon-influenza-virus-infection
#4
Milton Thomas, Max Pierson, Tirth Uprety, Laihua Zhu, Zhiguang Ran, Chithra C Sreenivasan, Dan Wang, Ben Hause, David H Francis, Feng Li, Radhey S Kaushik
Influenza viruses infect the epithelial cells of the swine respiratory tract. Cell lines derived from the respiratory tract of pigs could serve as an excellent in vitro model for studying the pathogenesis of influenza viruses. In this study, we examined the replication of influenza viruses in the MK1-OSU cell line, which was clonally derived from pig airway epithelium. MK1-OSU cells expressed both cytokeratin and vimentin proteins and displayed several sugar moieties on the cell membrane. These cells also expressed both Sial2-3Gal and Sial2-6Gal receptors and were susceptible to swine influenza A, but not to human B and C viruses...
June 7, 2018: Viruses
https://www.readbyqxmd.com/read/29867431/anti-mda5-antibody-positive-dermatomyositis-presenting-with-cellulitis-like-erythema-on-the-mandible-as-an-initial-symptom
#5
Yuki Hattori, Kanako Matsuyama, Tomoko Takahashi, En Shu, Hiroyuki Kanoh, Mariko Seishima
Panniculitis is an uncommon skin eruption observed in patients with dermatomyositis (DM)/clinically amyopathic dermatomyositis (CADM), especially in anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM. We present here a 51-year-old Japanese woman with an anti-MDA5 antibody-positive DM who initially had cellulitis-like erythema on her right mandible. Histopathological findings showed a subcutaneous lobular infiltration of lymphocytes. The patient developed typical skin eruptions of DM/CADM, rapidly progressive interstitial lung disease, and severe muscle weakness 2 weeks after the first visit...
May 2018: Case Reports in Dermatology
https://www.readbyqxmd.com/read/29864504/porcine-circovirus-2-infection-induces-ifn%C3%AE-expression-through-increased-expression-of-genes-involved-in-rig-i-and-irf7-signaling-pathways
#6
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
https://www.readbyqxmd.com/read/29770465/expression-of-myxovirus-resistance-protein-a-a-possible-marker-of-muscle-disease-activity-and-autoantibody-specificities-in-juvenile-dermatomyositis
#7
Sirisucha Soponkanaporn, Claire T Deakin, Peter W Schutz, Lucy R Marshall, Shireena A Yasin, Cerise M Johnson, Erdal Sag, Sarah L Tansley, Neil J McHugh, Lucy R Wedderburn, Thomas S Jacques
AIMS: To evaluate the relationship between expression of Myxovirus-resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in JDM patients. Also, another aim was to investigate whether the expression of MxA is related with myositis-specific autoantibodies (MSA) status in JDM patients. METHODS: 103 patients (median aged 6.3, IQR 0.5-15.9) enrolled in the Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS). Muscle biopsies were stained with MxA and scored...
May 16, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29769705/possible-role-of-the-nipah-virus-v-protein-in-the-regulation-of-the-interferon-beta-induction-by-interacting-with-ubx-domain-containing-protein1
#8
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
https://www.readbyqxmd.com/read/29769346/porcine-deltacoronavirus-accessory-protein-ns6-antagonizes-ifn-%C3%AE-production-by-interfering-with-the-binding-of-rig-i-mda5-to-double-stranded-rna
#9
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
https://www.readbyqxmd.com/read/29760190/tick-borne-encephalitis-virus-nonstructural-protein-ns5-induces-rantes-expression-dependent-on-the-rna-dependent-rna-polymerase-activity
#10
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
https://www.readbyqxmd.com/read/29758486/poly-i-c-and-lps-induce-distinct-immune-responses-by-ovarian-stromal-fibroblasts
#11
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
https://www.readbyqxmd.com/read/29753657/irf-1-rig-i-and-mda5-display-potent-antiviral-activities-against-norovirus-coordinately-induced-by-different-types-of-interferons
#12
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
https://www.readbyqxmd.com/read/29751011/differential-innate-immune-responses-induced-by-classical-and-variant-infectious-bronchitis-viruses-in-specific-pathogen-free-chicks
#13
Rajesh Chhabra, Christopher Ball, Julian Chantrey, Kannan Ganapathy
Avian infectious bronchitis virus (IBV) continues to cause serious economic losses in global chicken production. Concurrent circulation of both classic and variant IBVs have been identified in most parts of the world, raising major challenges to global prevention and control efforts. Therefore, immunopathogenesis, particularly early host responses, needs to be better understood for effective control of diseases caused by different strains of IBVs. We investigated differing immunopathogenesis in chickens following infection with IS/885/00-like (885), QX-like (QX) and M41 IBV strains...
May 8, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29740948/astrocytes-an-active-player-in-aicardi-gouti%C3%A3-res-syndrome
#14
Sunetra Sase, Asako Takanohashi, Adeline Vanderver, Akshata Almad
Aicardi-Goutières syndrome (AGS) is an early-onset, autoimmune and genetically heterogeneous disorder with severe neurologic injury. Molecular studies have established that autosomal recessive mutations in one of the following genes are causative: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1 and IFIH1/MDA5. The phenotypic presentation and pathophysiology of AGS is associated with over-production of the cytokine Interferon-alpha (IFN-α) and its downstream signaling, characterized as type I interferonopathy...
May 2018: Brain Pathology
https://www.readbyqxmd.com/read/29713969/rituximab-for-refractory-rapidly-progressive-interstitial-lung-disease-related-to-anti-mda5-antibody-positive-amyopathic-dermatomyositis
#15
Ho So, Victor Tak Lung Wong, Virginia Weng Nga Lao, Hin Ting Pang, Ronald Man Lung Yip
To report our experience in using rituximab (RTX) for treating refractory rapidly progressive interstitial lung disease (RP-ILD) complicating anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive amyopathic dermatomyositis (ADM). Medical records of four ADM patients with refractory RP-ILD treated with RTX therapy were reviewed retrospectively. All four patients were tested positive for anti-MDA5 Ab and failed to respond to high-dose systemic steroid and other intensive immunosuppressive therapies...
July 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29706970/h7n9-avian-influenza-virus-is-efficiently-transmissible-and-induces-an-antibody-response-in-chickens
#16
Peirong Jiao, Yafen Song, Jianni Huang, Chengwei Xiang, Jin Cui, Siyu Wu, Nannan Qu, Nianchen Wang, Guowen Ouyang, Ming Liao
H7N9 viruses pose a threat to human health and they are no less harmful to the poultry industry than the H5N1 avian influenza viruses. However, the pathogenesis, transmissibility, and the host immune response of the H7N9 virus in chickens and mice remain unclear. In this study, we found that H7N9 viruses replicated in multiple organs of the chicken and viral shedding persisted up to 30 days postinoculation (DPI). The viruses were efficiently transmitted between chickens through direct contact. Notably, chickens infected with H7N9 had high antibody levels throughout the entire observation period and their antibody response lasted for 30 DPI...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29696308/role-of-mda5-and-interferon-i-in-dendritic-cells-for-t-cell-expansion-by-anti-tumor-peptide-vaccines-in-mice
#17
Hussein Sultan, Juan Wu, Takumi Kumai, Andres M Salazar, Esteban Celis
Cytotoxic T lymphocytes (CTLs) are effective components of the immune system capable of destroying tumor cells. Generation of CTLs using peptide vaccines is a practical approach to treat cancer. We have previously described a peptide vaccination strategy that generates vast numbers of endogenous tumor-reactive CTLs after two sequential immunizations (prime-boost) using poly-ICLC adjuvant, which stimulates endosomal toll-like receptor 3 (TLR3) and cytoplasmic melanoma differentiation antigen 5 (MDA5). Dendritic cells (DCs) play an important role not only in antigen presentation but are critical in generating costimulatory cytokines that promote CTL expansion...
April 25, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29688572/enhanced-expression-of-ifi16-and-rig-i-in-human-third-trimester-placentas-following-hsv-1-infection
#18
Agnieszka Jabłońska, Mirosława Studzińska, Patrycja Suski, Jarosław Kalinka, Edyta Paradowska
The innate immune response in the placenta depends on the ability of maternal immune cells and fetal trophoblast cells to detect and eliminate invading pathogens through germline-encoded pattern recognition receptors (PRRs). In the present study, we analyzed the transcripts and protein expression of IFI16, MDA5, RIG-I, and TLR3 in third-trimester human placentas and investigated cytokine profiles generated during herpes simplex type 1 (HSV-1) infection. Decidual and chorionic villous biopsies (38-42 week of gestation) were obtained from healthy women immediately after a cesarean section...
April 24, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29686409/vibrio-vulnificus-quorum-sensing-molecule-cyclo-phe-pro-inhibits-rig-i-mediated-antiviral-innate-immunity
#19
Wooseong Lee, Seung-Hoon Lee, Minwoo Kim, Jae-Su Moon, Geon-Woo Kim, Hae-Gwang Jung, In Hwang Kim, Ji Eun Oh, Hi Eun Jung, Heung Kyu Lee, Keun Bon Ku, Dae-Gyun Ahn, Seong-Jun Kim, Kun-Soo Kim, Jong-Won Oh
The recognition of pathogen-derived ligands by pattern recognition receptors activates the innate immune response, but the potential interaction of quorum-sensing (QS) signaling molecules with host anti-viral defenses remains largely unknown. Here we show that the Vibrio vulnificus QS molecule cyclo(Phe-Pro) (cFP) inhibits interferon (IFN)-β production by interfering with retinoic-acid-inducible gene-I (RIG-I) activation. Binding of cFP to the RIG-I 2CARD domain induces a conformational change in RIG-I, preventing the TRIM25-mediated ubiquitination to abrogate IFN production...
April 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29679565/activation-of-tlr3-and-its-adaptor-ticam-1-increases-mir-21-levels-in-extracellular-vesicles-released-from-human-cells
#20
Yoshimi Fukushima, Masaaki Okamoto, Kana Ishikawa, Takahisa Kouwaki, Hirotake Tsukamoto, Hiroyuki Oshiumi
Pattern-recognition receptors (PRRs) recognizes viral RNAs and trigger the innate immune responses. Toll-like receptor 3 (TLR3), a PRR, recognizes viral double-stranded RNA (dsRNA) in endolysosomes, whereas cytoplasmic dsRNA is sensed by another PRR, MDA5. TLR3 and MDA5 utilize TICAM-1 and MAVS, respectively, to trigger the signal for inducing innate immune responses. Extracellular vesicles (EVs) include the exosomes and microvesicles; an accumulating body of evidence has shown that EVs delivers functional RNA, such as microRNAs (miRNAs), to other cells and thus mediate intercellular communications...
June 7, 2018: Biochemical and Biophysical Research Communications
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