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interferon lambda

Xue Gao, Yong-Yi Yuan, Qiong-Fen Lin, Jin-Cao Xu, Wei-Qian Wang, Yue-Hua Qiao, Dong-Yang Kang, Dan Bai, Feng Xin, Sha-Sha Huang, Shi-Wei Qiu, Li-Ping Guan, Yu Su, Guo-Jian Wang, Ming-Yu Han, Yi Jiang, Han-Kui Liu, Pu Dai
Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism...
February 16, 2018: Journal of Medical Genetics
Meihua Ran, Jiegang Huang, Hao Liang, Junjun Jiang, Bingyu Liang, Chuanyi Ning, Ning Zang, Weibo Liao, Huifang Liu, Fengxiang Qin, Quanlue Yang, Wenzhe Ho, Li Ye, Hui Chen
AIM: Alcohol could compromise the anti-hepatitis C virus (HCV) function of interferon-alpha (IFN-α). However, little information is available about the effect of alcohol on interferon-lambda (IFN-λ, type III IFN), a novel candidate for development of therapy for HCV infection. METHODS: Huh7 cells were infected with HCV JFH-1 virus, then treated with alcohol and/or IFN-λ1. RT-PCR and western blot were used to detect the levels of HCV and key cellular factors. Overexpression or silencing expression was performed to verify the role of key factors in alcohol-attenuated anti-HCV function of IFN-λ1...
February 15, 2018: Journal of Medical Virology
A Kalinowski, B T Galen, I F Ueki, Y Sun, A Mulenos, A Osafo-Addo, B Clark, J Joerns, W Liu, J A Nadel, C S Dela Cruz, J L Koff
Respiratory syncytial virus (RSV) persists as a significant human pathogen that continues to contribute to morbidity and mortality. In children, RSV is the leading cause of lower respiratory tract infections, and in adults RSV causes pneumonia and contributes to exacerbations of chronic lung diseases. RSV induces airway epithelial inflammation by activation of the epidermal growth factor receptor (EGFR), a tyrosine kinase receptor. Recently, EGFR inhibition was shown to decrease RSV infection, but the mechanism(s) for this effect are not known...
February 7, 2018: Mucosal Immunology
Salah Elias, Elizabeth J Robertson, Elizabeth K Bikoff, Arne W Mould
The transcriptional repressor Blimp-1 originally cloned as a silencer of type I interferon (IFN)-β gene expression controls cell fate decisions in multiple tissue contexts. Conditional inactivation in the mammary gland was recently shown to disrupt epithelial cell architecture. Here we report that Blimp-1 regulates expression of viral defense, IFN signaling and MHC class I pathways, and directly targets the transcriptional activator Stat1. Blimp-1 functional loss in 3D cultures of mammary epithelial cells (MECs) results in accumulation of dsRNA and expression of type III IFN-λ...
January 10, 2018: Scientific Reports
Hamid Akbarshahi, Mandy Menzel, Sangeetha Ramu, Irma Mahmutovic Persson, Leif Bjermer, Lena Uller
BACKGROUND: Impaired antiviral interferon expression may be involved in asthma exacerbations commonly caused by rhinovirus infections. Allergy is a known risk factor for viral-induced asthma exacerbation, but little is known whether allergens may affect interferon responses. OBJECTIVE: Our hypothesis is that house dust mite (HDM) impairs viral stimulus-induced antiviral signalling. METHODS: Experimental asthma exacerbations were produced in vitro in human bronchial epithelial cells (HBECs) and in mice by using sequential challenges with HDM and a viral infection mimic, Poly(I:C)...
January 10, 2018: Allergy
S Barathiraja, P A V Gangadhara, V Umapathi, H J Dechamma, G R Reddy
Interferon lambda-3 (IFNλ3) which is also known as IL28B is a member of type III Interferons which are structurally and genetically different from type I Interferons. These Interferons induce signal transduction pathways similar to type I Interferons which results in the activation of Interferon Stimulated Genes (ISGs). This group of Interferons are tissue specific and reported to have antiviral activity. In the present communication, we report the expression of bovine IFNλ3 gene (coding for the mature protein) in Pichia pastoris, purification of the expressed protein and evaluation of its biological activity...
December 23, 2017: Protein Expression and Purification
Avraham Bayer, Nicholas J Lennemann, Yingshi Ouyang, Elena Sadovsky, Megan A Sheridan, R Michael Roberts, Carolyn B Coyne, Yoel Sadovsky
INTRODUCTION: Cultured primary human trophoblasts (PHT), derived from term placentas, are relatively resistant to infection by diverse viruses. The resistance can be conferred to non-trophoblastic cells by pre-exposing them to medium that was conditioned by PHT cells. This antiviral effect is mediated, at least in part, by microRNAs (miRNA) expressed from the chromosome 19 microRNA cluster (C19MC). Recently we showed that PHT cells and cells pre-exposed to PHT medium are also resistant to infection by Zika virus (ZIKV), an effect mediated by the constitutive release of the type III interferons (IFN) IFN lambda-1 and IFN lambda-2 in trophoblastic medium...
January 2018: Placenta
Fabiana Cannella, Carolina Scagnolari, Maura Statzu, Ilaria Sciandra, Nadia Recine, Gabriella d'Ettorre, Guido Antonelli, Alessandra Pierangeli
Interferon (IFN) lambdas are important specific components of the mucosal innate immune response. The IFN lambda 4 (IFNL4) dinucleotide polymorphism (ΔG/TT) determines the IFN lambdas and related Interferon-stimulated genes activation, in HCV and other chronic infections. Our group first reported that IFN Lambda response was impaired in high-risk Human Papillomavirus (HPV) cervical infections and in precancerous lesions. Accordingly, we sought to evaluate the possible role of the IFNL4 polymorphism in determining HPV infection outcome...
December 14, 2017: Virus Genes
Ivan Zanoni, Francesca Granucci, Achille Broggi
Type III interferons (IFNs) (or IFN-λ) are the latest addition to the IFN family. Even though they share little protein homology with type I IFN, both exhibit remarkable functional similarities: each can be induced in response to viral infections, and both lead to Janus kinases (JAK) and signal transducer and activator of transcription (STAT) activation. The JAK/STAT pathway induces antiviral responses and IFN-stimulated gene transcription. However, despite the similarities in their effector functions with type I IFNs, IFN-λ also has a non-redundant role in protecting barrier organs: epithelial cells preferentially produce IFN-λ rather than type I IFNs; and interferon lambda receptor 1 (IFNLR1), the specific receptor for IFN-λ, is highly expressed on cells of epithelial lineage...
2017: Frontiers in Immunology
Brad R Rosenberg, Catherine A Freije, Naoko Imanaka, Spencer T Chen, Jennifer L Eitson, Rachel Caron, Skyler A Uhl, Marija Zeremski, Andrew Talal, Ira M Jacobson, Charles M Rice, John W Schoggins
Polymorphisms at IFNL4 strongly influence spontaneous resolution and interferon therapeutic response in hepatitis C virus (HCV) infection. In chronic HCV, unfavorable alleles are associated with elevated interferon stimulated gene (ISG) expression in the liver, but extrahepatic effects are less well characterized. We used RNA-Seq to examine whether IFNL4 genetic variation (rs368234815) modulates ISG expression in peripheral blood mononuclear cells (PBMC) during chronic HCV. ISG expression was elevated in unstimulated PBMC homozygous for the unfavorable ΔG IFNL4 variant; expression following IFNα stimulation was comparable across genotypes...
November 20, 2017: Journal of Infectious Diseases
R Pingwara, K Witt-Jurkowska, K Ulewicz, J Mucha, K Tonecka, Z Pilch, B Taciak, K Zabielska-Koczywas, M Mori, S Berardozzi, B Botta, T P Rygiel, M Krol
Myeloid-derived suppressor cells (MDSCs) support tumor development by stimulation of angiogenesis and immune response inhibition. In our previous study, we showed that interferon lambda 2 (IFN-λ2), secreted by MDSCs, enhances production of pro-angiogenic factors by cancer cells via phosphorylation of STAT3 and therefore promotes blood vessels formation. In the present study IFN-λ2 level was evaluated by ELISA in serum of tumor-bearing mice, whereas its expression in MDSCs isolated from the lungs with metastatic tumors and normal lungs was assessed by qPCR...
August 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Shingo Nakamoto, Fumio Imazeki, Tatsuo Kanda, Shuang Wu, Masato Nakamura, Shin Yasui, Akinobu Tawada, Rintaro Mikata, Tetsuhiro Chiba, Makoto Arai, Osamu Yokosuka, Hiroshi Shirasawa
BACKGROUND: Genetic variation near the interferon lambda 3 (IFNL3) is known to be associated with response to pegylated interferon (pegIFN) and ribavirin combination therapy in patients with chronic hepatitis C virus (HCV) infection which is often accompanied by hepatic steatosis. AIMS: We examined whether this genetic variation is associated with host lipids and treatment response. METHODS: A total of 101 Japanese patients who had underwent liver biopsy before treatment with pegIFN and ribavirin for HCV genotype 1b infection were retrospectively analyzed for association between IFNL3 genotypes (rs8099917) and clinical factors including histopathological features of the liver...
2017: International Journal of Medical Sciences
Joana Rocha-Pereira, Sophie Jacobs, Sam Noppen, Eric Verbeken, Thomas Michiels, Johan Neyts
Human noroviruses are highly efficient in person to person transmission thus associated with explosive outbreaks of acute gastroenteritis. Outbreak control is limited to disinfection and isolation measures. Strategies to control the spread of noroviruses should be developed and models to study norovirus transmission will greatly facilitate this. Here, a mouse-to-mouse transmission model, in which mice develop acute murine norovirus (MNV)-induced diarrhea, was used to explore the role of interferon lambda (IFN-λ) in the control of a norovirus infection...
January 2018: Antiviral Research
Renata Wieczorek-Godlewska, Rafał Płoski, Agnieszka Perkowska-Ptasińska, Olga Tronina, Anna Sadowska, Marek Pacholczyk, Wojciech Lisik, Magdalena Durlik
AIM OF THE STUDY: Aim of the study was to assess the impact of the recipient and donor interferon lambda-3 (IFNL3) single-nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 on the course of hepatitis C virus (HCV) reinfection following liver transplantation. MATERIAL AND METHODS: The study involved 141 subjects after liver transplantation for HCV-induced cirrhosis, performed between 2000 and 2015. It assessed the impact of both SNPs on the outcomes of interferon/ribavirin (IFN/RBV) treatment following transplantation, HCV viral load, laboratory test results, histological lesions in the liver graft, the risk of acute rejection, and the development of hepatocellular carcinoma (HCC) in patient's own liver...
September 2017: Clinical and Experimental Hepatology
Y T Jia, X H Duan, Z X Yang, Y H Su
No abstract text is available yet for this article.
July 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Evangelos Andreakos, Maria Salagianni, Ioanna E Galani, Ourania Koltsida
Type III interferons (IFNs), also termed lambda IFNs (IFNλs) or interleukins-28/29, constitute a new addition to the IFN family. They are induced upon infection and are particularly abundant at barrier surfaces, such as the respiratory and gastrointestinal tracts. Although they signal through a unique heterodimeric receptor complex comprising IFNLR1 and IL10RB, they activate a downstream signaling pathway remarkably similar to that of type I IFNs and share many functions with them. Yet, they also have important differences which are only now starting to unfold...
2017: Frontiers in Immunology
Linh Thuy Nguyen, Dzung Van Nguyen, Michael J Carr, William W Hall, Lan Anh Nguyen
Globally, hepatitis C virus (HCV) is one of the major causes of hepatocellular carcinoma and liver cirrhosis. For clinical decision making, genetic variation in the interferon-λ (IFNL) cluster has been utilised as a baseline predictor of natural and interferon-based treatment-induced viral clearance. In Vietnam, where HCV genotypes 1 (g1) and g6 predominate, no prior studies have been conducted investigating associations of IFNL3/4 polymorphisms with spontaneous clearance (SC) or HCV viral load (VL) in chronic infection...
October 11, 2017: Archives of Virology
Andrea Saul Costa, Simone Agostini, Franca Rosa Guerini, Roberta Mancuso, Milena Zanzottera, Enrico Ripamonti, Vittorio Racca, Raffaello Nemni, Mario Clerici
Herpes simplex virus type 1 (HSV-1) has long been suspected to play a role in Alzheimer's disease (AD), the most common form of dementia. IFN-lambda (IFN-λ) is one of the key cytokine in innate antiviral defenses and, in particular, has an appreciable antiviral activity against HSV-1 infection. IFN-λ expression is regulated by the interaction between two different proteins: Mediator Complex 23 (MED23) and Interferon-Responsive Transcription Factor 7 (IRF7); single nucleotide polymorphisms (SNPs) in these genes as well as in IFNL3 were shown to be differently distributed in AD patients...
2017: Journal of Alzheimer's Disease: JAD
Sanghyun Lee, Craig B Wilen, Anthony Orvedahl, Broc T McCune, Ki-Wook Kim, Robert C Orchard, Stefan T Peterson, Timothy J Nice, Megan T Baldridge, Herbert W Virgin
Cellular tropism during persistent viral infection is commonly conferred by the interaction of a viral surface protein with a host receptor complex. Norovirus, the leading global cause of gastroenteritis, can be persistently shed during infection, but its in vivo cellular tropism and tropism determinants remain unidentified. Using murine norovirus (MNoV), we determine that a small number of intestinal epithelial cells (IECs) serve as the reservoir for fecal shedding and persistence. The viral non-structural protein NS1, rather than a viral surface protein, determines IEC tropism...
October 11, 2017: Cell Host & Microbe
Tanja Blumer, Mairene Coto-Llerena, Francois H T Duong, Markus H Heim
Type I (α and β) and type III (λ) IFNs are induced upon viral infection through host sensory pathways that activate IFN regulatory factors (IRFs) and nuclear factor κB. Secreted IFNs induce autocrine and paracrine signaling through the JAK-STAT pathway, leading to the transcriptional induction of hundreds of IFN-stimulated genes, among them sensory pathway components such as cGAS, STING, RIG-I, MDA5, and the transcription factor IRF7, which enhance the induction of IFN-αs and IFN-λs. This positive feedback loop enables a very rapid and strong host response that, at some point, has to be controlled by negative regulators to maintain tissue homeostasis...
October 27, 2017: Journal of Biological Chemistry
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