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interferon lambda

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https://www.readbyqxmd.com/read/28514692/interferon-%C3%AE-mediates-non-redundant-front-line-antiviral-protection-against-influenza-virus-infection-without-compromising-host-fitness
#1
Ioanna E Galani, Vasiliki Triantafyllia, Evridiki-Evangelia Eleminiadou, Ourania Koltsida, Athanasios Stavropoulos, Maria Manioudaki, Dimitris Thanos, Sean E Doyle, Sergei V Kotenko, Kalliopi Thanopoulou, Evangelos Andreakos
Lambda interferons (IFNλs) or type III IFNs share homology, expression patterns, signaling cascades, and antiviral functions with type I IFNs. This has complicated the unwinding of their unique non-redundant roles. Through the systematic study of influenza virus infection in mice, we herein show that IFNλs are the first IFNs produced that act at the epithelial barrier to suppress initial viral spread without activating inflammation. If infection progresses, type I IFNs come into play to enhance viral resistance and induce pro-inflammatory responses essential for confronting infection but causing immunopathology...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28513591/zinc-is-a-potent-and-specific-inhibitor-of-ifn-%C3%AE-3-signalling
#2
Scott A Read, Kate S O'Connor, Vijay Suppiah, Chantelle L E Ahlenstiel, Stephanie Obeid, Kristina M Cook, Anthony Cunningham, Mark W Douglas, Philip J Hogg, David Booth, Jacob George, Golo Ahlenstiel
Lambda interferons (IFNL, IFN-λ) are pro-inflammatory cytokines important in acute and chronic viral infection. Single-nucleotide polymorphisms rs12979860 and rs8099917 within the IFNL gene locus predict hepatitis C virus (HCV) clearance, as well as inflammation and fibrosis progression in viral and non-viral liver disease. The underlying mechanism, however, is not defined. Here we show that the rs12979860 CC genotype correlates with increased hepatic metallothionein expression through increased systemic zinc levels...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28475945/emerging-concepts-for-the-treatment-of-hepatitis-delta
#3
REVIEW
Menashe Elazar, Jeffrey S Glenn
Hepatitis delta virus (HDV) causes the most severe form of human viral hepatitis and is associated with a higher risk of cirrhosis, liver decompensation and liver cancer. Interferon alpha is the only agent that has demonstrated efficacy to date, although response rates are low and it is associated with significant side effects. A better understanding of the relevant molecular virology has resulted in the identification of new candidate targets. Future therapeutic options are rapidly evolving as several new agents have entered clinical development, including the entry inhibitor myrcludex-B, the nucleic acid polymer REP2139-Ca inhibiting HBV surface antigen secretion, the farnesyltransferase inhibitor lonafarnib that targets virus assembly, and a better tolerated interferon-interferon lambda...
May 2, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28467457/a-prognostic-model-for-development-of-significant-liver-fibrosis-in-hiv-hepatitis-c-co-infection
#4
Nasheed Moqueet, Cynthia Kanagaratham, M John Gill, Mark Hull, Sharon Walmsley, Danuta Radzioch, Sahar Saeed, Robert W Platt, Marina B Klein
BACKGROUND: Liver fibrosis progresses rapidly in HIV-Hepatitis C virus (HCV) co-infected individuals partially due to heightened inflammation. Immune markers targeting stages of fibrogenesis could aid in prognosis of fibrosis. METHODS: A case-cohort study was nested in the prospective Canadian Co-infection Cohort (n = 1119). HCV RNA positive individuals without fibrosis, end-stage liver disease or chronic Hepatitis B at baseline (n = 679) were eligible. A random subcohort (n = 236) was selected from those eligible...
2017: PloS One
https://www.readbyqxmd.com/read/28397468/association-of-serum-interleukin-28b-with-clinical-features-laboratory-values-and-radiographic-score-in-rheumatoid-arthritis-patients
#5
Cheng Lv, Qiong-Jie Chang, Feng Zhao, Li-Qi Bi, Ping Li
BACKGROUND: Interleukin-28B (IL-28B) is a member of the interferon lambda family (also known as type III interferons), it has already been studied in many diseases, but it has almost never been studied in rheumatoid arthritis (RA). With this background, we determined the serum levels of IL-28B in RA patients and investigated its clinical significances. METHODS: IL-28B levels were measured by enzyme-linked immunosorbent assay (ELISA) in 80 RA patients and 80 healthy controls...
April 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28394351/genome-to-genome-analysis-highlights-the-effect-of-the-human-innate-and-adaptive-immune-systems-on-the-hepatitis-c-virus
#6
M Azim Ansari, Vincent Pedergnana, Camilla L C Ip, Andrea Magri, Annette Von Delft, David Bonsall, Nimisha Chaturvedi, Istvan Bartha, David Smith, George Nicholson, Gilean McVean, Amy Trebes, Paolo Piazza, Jacques Fellay, Graham Cooke, Graham R Foster, Emma Hudson, John McLauchlan, Peter Simmonds, Rory Bowden, Paul Klenerman, Eleanor Barnes, Chris C A Spencer
Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. Here we use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals who were chronically infected with HCV, predominantly genotype 3. We show that both alleles of genes encoding human leukocyte antigen molecules and genes encoding components of the interferon lambda innate immune system drive viral polymorphism...
May 2017: Nature Genetics
https://www.readbyqxmd.com/read/28342759/activation-of-epithelial-stat1-by-interleukin-28-controls-mucosal-healing-in-mice-with-colitis-and-is-increased-in-mucosa-of-patients-with-inflammatory-bowel-disease
#7
Mircea T Chiriac, Barbara Buchen, Alexandra Wandersee, Gheorghe Hundorfean, Claudia Günther, Yvonne Bourjau, Sean E Doyle, Benjamin Frey, Arif B Ekici, Christian Büttner, Benno Weigmann, Raja Atreya, Stefan Wirtz, Christoph Becker, Jürgen Siebler, Markus F Neurath
BACKGROUND & AIMS: We investigated the roles of interleukin 28A (also called IL28A or interferon lambda 2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing. METHODS: Colitis was induced in C57BL/6JCrl mice (controls), mice with intestinal epithelial cell-specific disruption of Stat1 (Stat1IEC-KO), mice with disruption of the interferon lambda receptor 1 gene (Il28ra-/-), and mice with disruption of the interferon regulatory factor 3 gene (Irf3-/-), with or without disruption of Irf7 (Irf7-/-)...
March 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28315743/treatment-with-peg-ifn-and-ribavirin-in-patients-with-chronic-hepatitis-c-low-grade-of-hepatic-fibrosis-genotype-1-and-4-and-favorable-ifnl3-genotype-a-pharmacogenetic-prospective-study
#8
Lucio Boglione, Chiara Simona Cardellino, Jessica Cusato, Amedeo De Nicolò, Giuseppe Cariti, Giovanni Di Perri, Antonio D'Avolio
The new direct-acting antivirals agents (DAAs) rapidly changed the treatment approach in chronic hepatitis C (CHC); however, the interferon (IFN)-free therapies availability is currently different in some countries, due to higher costs of these drugs. Naïve treated patients, who are not eligible for IFN-free therapies, could be selected for standard dual treatment with pegylated (PEG)-IFN and ribavirin (RBV), through IFN lambda 3 gene polymorphisms and fibrosis stage evaluation. Inclusion criteria were: naïve treated CHC patients with GT1 or GT4, without major contraindication to PEG-IFN or RBV, with fibrosis stage F0-F2 and IFNL3 rs8099917/rs12979860 TT/CC genotypes...
March 16, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28293236/interferon-lambda-modulating-immunity-in-infectious-diseases
#9
REVIEW
Mohammedyaseen Syedbasha, Adrian Egli
Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28282271/safety-and-efficacy-of-pegylated-interferon-lambda-ribavirin-and-daclatasvir-in-hcv-and-hiv-coinfected-patients
#10
Mark Nelson, Rafael Rubio, Adriano Lazzarin, Svetlana Romanova, Annie Luetkemeyer, Brian Conway, Jean-Michel Molina, Dong Xu, Subasree Srinivasan, Simon Portsmouth
To evaluate the efficacy and safety of pegylated interferon-lambda-1a (Lambda)/ribavirin (RBV)/daclatasvir (DCV) for treatment of patients coinfected with chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Treatment-naive patients were assigned to cohort A [HCV genotype (GT)-2 or -3] or cohort B [HCV GT-1(a or b) or -4]. All patients received Lambda/RBV/DCV for the first 12 weeks; cohort A received Lambda/RBV for an additional 12 weeks, followed by 24 weeks of follow-up, and cohort B received response-guided therapy...
March 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28274837/a-novel-method-for-detection-of-ifn-lambda-3-binding-to-cells-for-quantifying-ifn-lambda-receptor-expression
#11
Deanna M Santer, Gillian E S Minty, Adil Mohamed, Lesley Baldwin, Rakesh Bhat, Michael Joyce, Adrian Egli, D Lorne J Tyrrell, Michael Houghton
Type III interferons (IFN-lambdas) are important antiviral cytokines that also modulate immune responses acting through a unique IFN-λR1/IL-10R2 heterodimeric receptor. Conflicting data has been reported for which cells express the IFN-λR1 subunit and directly respond to IFN-λs. In this study we developed a novel method to measure IFN-λ3 binding to IFN-λR1/IL-10R2 on the surface of cells and relate this to a functional readout of interferon stimulated gene (ISG) activity in various cell lines. We show that Huh7...
March 6, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28263098/type-iii-interferons-and-rheumatoid-arthritis-correlation-between-interferon-lambda-1-interleukin-29-and-antimutated-citrullinated-vimentin-antibody-levels
#12
Diana Castillo-Martínez, Maribel Juarez, Mariana Patlán, Araceli Páez, Felipe Massó, Luis M Amezcua-Guerra
AIM: To assess serum type III or lambda (λ) interferons (IFN) levels and its clinical and laboratory associations in rheumatoid arthritis (RA). METHODS: A cross-sectional study including 43 patients with RA (86% females; age 45.3 ± 10.3 years) and 43 healthy individuals was performed. Clinical data including disease activity, acute-phase reactants, rheumatoid factor and anticyclic citrullinated peptide (anti-CCP) antibodies were collected. Serum IFNλ1, IFNλ2, IFNλ3, CXCL8 and anti-mutated citrullinated vimentin (anti-MCV) antibody levels were measured...
March 2017: Autoimmunity
https://www.readbyqxmd.com/read/28255563/the-role-of-type-iii-interferons-in-hepatitis-c-virus-infection-and-therapy
#13
REVIEW
Janina Bruening, Bettina Weigel, Gisa Gerold
The human interferon (IFN) response is a key innate immune mechanism to fight virus infection. IFNs are host-encoded secreted proteins, which induce IFN-stimulated genes (ISGs) with antiviral properties. Among the three classes of IFNs, type III IFNs, also called IFN lambdas (IFNLs), are an essential component of the innate immune response to hepatitis C virus (HCV). In particular, human polymorphisms in IFNL gene loci correlate with hepatitis C disease progression and with treatment response. To date, the underlying mechanisms remain mostly elusive; however it seems clear that viral infection of the liver induces IFNL responses...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28250263/lambda-interferons-inhibit-herpes-simplex-virus-type-2-replication-in-human-cervical-epithelial-cells-through-activation-of-jak-stat-pathway
#14
Zhu Li, Xuan Lu, Yufan Zhu, Pengfei Cheng, Shi Liu, Yi Zhang, Jingfeng Tang, Sijun Yang, Li Zhou
Herpes Simplex Virus Type 2 (HSV-2) is associated with a variety of diseases, resulting in world-wide health problems. Our early study showed that lambda-interferons (IFN-λs) induced by activation of the toll-like receptors 3/ retinoic acid-inducible protein I (TLR3/RIG-I) signaling pathways contribute to inhibition of HSV-2 replication in the human cervical epithelial cells. However, anti-HSV-2 mechanisms and specific differences in signaling transduction by different IFN-λs in human cervical epithelial cells are unclear...
February 28, 2017: Japanese Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28122304/synergy-with-interferon-lambda-3-and-sorafenib-suppresses-hepatocellular-carcinoma-proliferation
#15
Yuke Yan, Liang Wang, Jingjing He, Pengcheng Liu, Xi Lv, Yawu Zhang, Xiaodong Xu, Lingyi Zhang, Youcheng Zhang
Hepatocellular carcinoma (HCC) is a common and fatal malignancy of the liver. Sorafenib is a small molecule multikinase inhibitor that acts against different cancer cell lines and is used for the treatment of HCC. However, some advanced HCC patients fail to respond to sorafenib, and those who do lack a meaningful clinical benefit. Interferon-lambda 3 (IFN-λ3) is a type III interferon with antiviral, antiproliferative, and immunomodulatory functions. Here, we evaluated the use of IFN-λ3 as an adjuvant treatment with sorafenib in HCC...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28109912/ifn-lambda-preferably-inhibits-pedv-infection-of-porcine-intestinal-epithelial-cells-compared-with-ifn-alpha
#16
Lin Li, Fang Fu, Mei Xue, Weiye Chen, Jin Liu, Hongyan Shi, Jianfei Chen, Zhigao Bu, Li Feng, Pinghuang Liu
In contrast to type I interferons that target various types of cells and organs, interferon lambda (IFN-L) primarily acts on mucosal epithelial cells and exhibits robust antiviral activity within the mucosal surface. Porcine epidemic diarrhea virus (PEDV), which causes high morbidity and mortality in piglets, is an enteropathogenic coronavirus with economic importance. Here, we demonstrated that both recombinant porcine IFN-L1 (rpIFN-L1) and rpIFN-L3 have powerful antiviral activity against PEDV infection of both Vero E6 cells and the intestinal porcine epithelial cell line J2 (IPEC-J2)...
April 2017: Antiviral Research
https://www.readbyqxmd.com/read/28077655/expression-of-ifnlr1-on-intestinal-epithelial-cells-is-critical-to-the-antiviral-effects-of-interferon-lambda-against-norovirus-and-reovirus
#17
Megan T Baldridge, Sanghyun Lee, Judy J Brown, Nicole McAllister, Kelly Urbanek, Terence S Dermody, Timothy J Nice, Herbert W Virgin
Lambda interferon (IFN-λ) has potent antiviral effects against multiple enteric viral pathogens, including norovirus and rotavirus, in both preventing and curing infection. Because the intestine includes a diverse array of cell types, however, the cell(s) upon which IFN-λ acts to exert its antiviral effects is unclear. Here, we sought to identify IFN-λ-responsive cells by generation of mice with lineage-specific deletion of the receptor for IFN-λ, Ifnlr1 We found that expression of IFNLR1 on intestinal epithelial cells (IECs) in the small intestine and colon is required for enteric IFN-λ antiviral activity...
April 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28036111/hepatic-ifnl4-expression-is-associated-with-non-response-to-interferon-based-therapy-through-the-regulation-of-basal-interferon-stimulated-gene-expression-in-chronic-hepatitis-c-patients
#18
Miyako Murakawa, Yasuhiro Asahina, Fukiko Kawai-Kitahata, Mina Nakagawa, Sayuri Nitta, Satoshi Otani, Hiroko Nagata, Shun Kaneko, Yu Asano, Tomoyuki Tsunoda, Masato Miyoshi, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Yasuhito Tanaka, Sayuki Iijima, Kaoru Tsuchiya, Namiki Izumi, Shuji Tohda, Mamoru Watanabe
Single nucleotide polymorphisms (SNPs) within or near interferon lambda 4 (IFNL4) gene located upstream of IFNL3 are associated with response to anti-HCV therapy both in interferon (IFN)-based and IFN-free regimens. IFNL4 encodes IFNλ4, a newly discovered type III IFN, and its expression is controlled by rs368234815-TT/ΔG, which is in strong linkage disequilibrium (LD) with other tag SNPs within or near IFNL4 such as rs12979860 and rs8099917. Intrahepatic expression levels of IFN-stimulated genes (ISGs) affect the responsiveness to IFNα and are also associated with IFNL4 genotype...
July 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/27986689/hla-b-57-and-ifnl4-related-polymorphisms-are-associated-with-protection-against-hiv-1-disease-progression-in-controllers
#19
B Dominguez-Molina, L Tarancon-Diez, S Hua, C Abad-Molina, E Rodriguez-Gallego, K Machmach, F Vidal, C Tural, S Moreno, J M Goñi, E Ramírez de Arellano, M Del Val, M F Gonzalez-Escribano, J Del Romero, C Rodriguez, L Capa, P Viciana, J Alcamí, X G Yu, B D Walker, Manuel Leal, M Lichterfeld, E Ruiz-Mateos
BACKGROUND: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4(+)T-cell decline. We investigated host genetic factors associated with protection against CD4(+)T-cell loss in HIV-1-controllers. METHODS: We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4(+)T-cells counts >500 cells/mm(3) for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4(+)T-cells counts <500 cells/mm(3) Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined...
December 16, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/27904617/the-interferon-lambda-4-rs368234815-predicts-treatment-response-to-pegylated-interferon-alpha-and-ribavirin-in-hemophilic-patients-with-chronic-hepatitis-c
#20
Maryam Keshvari, Seyed Moayed Alavian, Bita Behnava, Ali Pouryasin, Heidar Sharafi
BACKGROUND: A dinucleotide variant rs368234815 in interferon lambda 4 (IFNL4) gene was recently found to be associated with the hepatitis C virus (HCV) treatment response. This study aimed to assess the impact of IFNL4 rs368234815 polymorphism on treatment response to pegylated-IFN alpha (Peg-IFN-α) and ribavirin (RBV) in hemophilic patients with chronic hepatitis C (CHC). MATERIALS AND METHODS: In this retrospective study, 92 hemophilic patients with CHC who were treated with Peg-IFN-α/RBV were investigated...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
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