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IFITM3

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https://www.readbyqxmd.com/read/29356071/the-anti-inflammatory-ifitm-genes-ameliorate-colitis-and-partially-protect-from-tumorigenesis-by-changing-immunity-and-microbiota
#1
Zoya Alteber, Adi Sharbi-Yunger, Meirav Pevsner-Fischer, Dan Blat, Lior Roitman, Esther Tzehoval, Eran Elinav, Lea Eisenbach
Inflammation plays pivotal roles in different stages of tumor development. Screening for predisposing genetic abnormalities and understanding the roles these genes play in the crosstalk between immune and cancer cells will provide new targets for cancer therapy and prevention. The interferon inducible transmembrane (IFITM) genes are involved in pathogenesis of the gastro-intestinal tract. We aimed at delineating the role of IFITM3 in colonic epithelial homeostasis, inflammation and colitis-associated tumorigenesis using IFITM3-deficient mice...
December 13, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29306950/immune-consequences-of-in-vitro-infection-of-human-peripheral-blood-leukocytes-with-vesicular-stomatitis-virus
#2
Tomasz Tomczyk, Grażyna Wróbel, Radosław Chaber, Iwona Siemieniec, Egbert Piasecki, Małgorzata Krzystek-Korpacka, Beata U Orzechowska
BACKGROUND: Oncolytic vesicular stomatitis virus (VSV) can be delivered intravenously to target primary and metastatic lesions, but the interaction between human peripheral blood leukocytes (PBLs) and VSV remains poorly understood. Our study aimed to assess the overall immunological consequences of ex vivo infection of PBLs with VSV. METHODS: Phenotypic analysis of lymphocyte subsets and apoptosis were evaluated with flow cytometry. Caspase 3/7 activity was detected by luminescence assay...
January 6, 2018: Journal of Innate Immunity
https://www.readbyqxmd.com/read/29281729/histone-demethylase-lsd1-restricts-influenza-a-virus-infection-by-erasing-ifitm3-k88-monomethylation
#3
Jiaoyu Shan, Binbin Zhao, Zhao Shan, Jia Nie, Rong Deng, Rui Xiong, Andy Tsun, Weiqi Pan, Hanzhi Zhao, Ling Chen, Ying Jin, Zhikang Qian, Kawing Lui, Rui Liang, Dan Li, Bing Sun, Dimitri Lavillette, Ke Xu, Bin Li
The histone demethylase LSD1 has been known as a key transcriptional coactivator for DNA viruses such as herpes virus. Inhibition of LSD1 was found to block viral genome transcription and lytic replication of DNA viruses. However, RNA virus genomes do not rely on chromatin structure and histone association, and the role of demethylase activity of LSD1 in RNA virus infections is not anticipated. Here, we identify that, contrary to its role in enhancing DNA virus replication, LSD1 limits RNA virus replication by demethylating and activating IFITM3 which is a host restriction factor for many RNA viruses...
December 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29259856/the-expression-profile-of-ifitm-family-gene-in-rats
#4
Yanqin Lu, Qingli Zuo, Yao Zhang, Yanzhou Wang, Tianyou Li, Jinxiang Han
The interferon-inducible transmembrane proteins (IFITMs) are a family of small transmembrane proteins belonging to the interferon (IFN)-stimulated gene (ISG) superfamily and strongly induced by IFNs. In this paper, we studied the expression profile of IFITMs in 32 organ tissues. The IFITM mRNA expression profile showed that IFITM1, IFITM2 and IFITM3 were expressed in each tissue, especially, in spermatophore, spermaduct, testicle and epididymis. The expression of IFITM1, IFITM2 and IFITM3 showed a trend from high to low...
November 2017: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/29202190/lack-of-truncated-ifitm3-transcripts-in-cells-homozygous-for-the-rs12252-c-variant-that-is-associated-with-severe-influenza-infection
#5
Shokouh Makvandi-Nejad, Henry Laurenson-Schafer, LiLi Wang, Dannielle Wellington, Yan Zhao, Boquan Jin, Ling Qin, Kerry Kite, Hooman K Moghadam, Chaojun Song, Kevin Clark, Philip Hublitz, Alain R Townsend, Hao Wu, Andrew J McMichael, YongHong Zhang, Tao Dong
Interferon-induced transmembrane 3 (IFITM3) is known to restrict the entry of a range of enveloped viruses. The single nucleotide polymorphism rs12252-C within IFITM3 has been shown to be associated with severe influenza A virus infection. It has been suggested that rs12252-C results in expression of a truncated IFITM3 protein lacking the first 21 amino acids. By performing high-throughput RNA sequencing on primary dendritic cells and peripheral blood mononuclear cells isolated from pandemic H1N1 influenza and human immunodeficiency virus-1 (HIV-1) infected patients we show that full-length IFITM3 mRNA is dominantly expressed (>99%) across all rs12252 genotypes...
November 30, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29162141/more-than-meets-the-i-the-diverse-antiviral-and-cellular-functions-of-interferon-induced-transmembrane-proteins
#6
REVIEW
Guoli Shi, Olivier Schwartz, Alex A Compton
The first responders of human antiviral immunity are components of the intrinsic immune response that reside within each and every one of our cells. This cell-autonomous arsenal consists of nucleic acid sensors and antiviral effectors strategically placed by evolution to detect and restrict invading viruses. While some factors are present at baseline to allow for constant surveillance of the cell interior, others are upregulated by cytokines (such as interferons) that signal a viral infection underway in neighboring cells...
November 21, 2017: Retrovirology
https://www.readbyqxmd.com/read/29132684/interactions-between-lactobacilli-and-chicken-macrophages-induce-antiviral-responses-against-avian-influenza-virus
#7
Bahram Shojadoost, Raveendra R Kulkarni, Jennifer T Brisbin, Wanderley Quinteiro-Filho, Tamiru N Alkie, Shayan Sharif
Macrophages are an important cell type of the innate immune system that upon activation, can exert antiviral functions and also can induce virus-specific adaptive immune responses. Macrophage interaction with certain probiotic bacteria such as lactobacilli can enhance antiviral functions of these cells. We have previously shown that administration of lactobacilli to chickens can effectively augment immune response to vaccine antigens. Here, we investigated the effects of representative strains of three Lactobacillus species, L...
October 31, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/29121968/association-of-ifitm3-rs12252-polymorphisms-bmi-diabetes-and-hypercholesterolemia-with-mild-flu-in-an-iranian-population
#8
Parvaneh Mehrbod, Sana Eybpoosh, Fatemeh Fotouhi, Hadiseh Shokouhi Targhi, Vahideh Mazaheri, Behrokh Farahmand
BACKGROUND: IFITM3 has been suggested to be associated with infection in some ethnic groups. Diabetes and hypercholesterolemia are also important clinical conditions that can predispose individuals to infection. The aim of this study was to investigate the association of rs12252 C polymorphism, BMI, diabetes, and hypercholesterolemia with mild flu in an Iranian population. METHODS: We conducted a case-control study, including 79 mild flu and 125 flu-negative individuals attending primary care centers of three provinces of Iran (i...
November 9, 2017: Virology Journal
https://www.readbyqxmd.com/read/29079573/the-palmitoyltransferase-zdhhc20-enhances-interferon-induced-transmembrane-protein-3-ifitm3-palmitoylation-and-antiviral-activity
#9
Temet M McMichael, Lizhi Zhang, Mahesh Chemudupati, Jocelyn C Hach, Adam D Kenney, Howard C Hang, Jacob S Yount
Interferon-induced transmembrane protein 3 (IFITM3) is a cellular endosome- and lysosome-localized protein that restricts numerous virus infections. IFITM3 is activated by palmitoylation, a lipid posttranslational modification. Palmitoylation of proteins is primarily mediated by zinc finger DHHC domain-containing palmitoyltransferases (ZDHHCs), but which members of this enzyme family can modify IFITM3 is not known. Here, we screened a library of human cell lines individually lacking ZDHHCs 1-24, and found that IFITM3 palmitoylation and its inhibition of influenza virus infection remained strong in the absence of any single ZDHHC, suggesting functional redundancy of these enzymes in the IFITM3-mediated antiviral response...
October 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29078734/ovarian-cancer-stem-cells-unravelling-a-germline-connection
#10
Seema Chandrakant Parte, Andrei S Smolenkov, Surinder K Batra, Mariusz Z Ratajczak, Sham Sunder Kakar
Ovarian cancer is most lethal among gynaecological cancers with often fatal consequences due to lack of effective bio-markers and relapse which propels ovarian cancer research into unique directions to establish solid targeted therapeutics. 'Ovarian stem cells' expressing germline, pluripotent markers serve as novel paradigm with potential to address infertility, menopause and probably influence tumor initiation. Cancer stem cells (CSCs) pose vital role in tumor recurrence and hence it is extremely important to study them with respect to ovarian stem cells across various cancer stages and normal ovaries...
October 27, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29053189/pilot-screening-study-of-targeted-genetic-polymorphisms-for-association-with-seasonal-influenza-hospital-admission
#11
Tonia C Carter, Scott J Hebbring, Jixia Liu, Jonathan D Mosley, Christian M Shaffer, Lynn C Ivacic, Sarah Kopitzke, Elisha L Stefanski, Rob Strenn, Maria E Sundaram, Jennifer Meece, Murray H Brilliant, Jill M Ferdinands, Edward A Belongia
Host response to influenza is highly variable, suggesting a potential role of host genetic variation. To investigate the host genetics of severe influenza in a targeted fashion, 32 single nucleotide polymorphisms (SNPs) within viral immune response genes were evaluated for association with seasonal influenza hospitalization in an adult study population with European ancestry. SNP allele and genotype frequencies were compared between hospitalized influenza patients (cases) and population controls in a case-control study that included a discovery group (26 cases and 993 controls) and two independent, validation groups (one with 84 cases and 4,076 controls; the other with 128 cases and 9,187 controls)...
October 20, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28957419/interference-with-the-production-of-infectious-viral-particles-and-bimodal-inhibition-of-replication-are-broadly-conserved-antiviral-properties-of-ifitms
#12
Kevin Tartour, Xuan-Nhi Nguyen, Romain Appourchaux, Sonia Assil, Véronique Barateau, Louis-Marie Bloyet, Julien Burlaud Gaillard, Marie-Pierre Confort, Beatriz Escudero-Perez, Henri Gruffat, Saw See Hong, Marie Moroso, Olivier Reynard, Stéphanie Reynard, Elodie Decembre, Najate Ftaich, Axel Rossi, Nannan Wu, Frédérick Arnaud, Sylvain Baize, Marlène Dreux, Denis Gerlier, Glaucia Paranhos-Baccala, Viktor Volchkov, Philippe Roingeard, Andrea Cimarelli
IFITMs are broad antiviral factors that block incoming virions in endosomal vesicles, protecting target cells from infection. In the case of HIV-1, we and others reported the existence of an additional antiviral mechanism through which IFITMs lead to the production of virions of reduced infectivity. However, whether this second mechanism of inhibition is unique to HIV or extends to other viruses is currently unknown. To address this question, we have analyzed the susceptibility of a broad spectrum of viruses to the negative imprinting of the virion particles infectivity by IFITMs...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28857475/overexpression-of-ifitm3-predicts-poor-prognosis-in-stage-iia-esophageal-squamous-cell-carcinoma-after-ivor-lewis-esophagectomy
#13
Yang Jia, Zhaohua Xiao, Wenpeng Jiang, Gang Chen, Zhou Wang
BACKGROUND: Recent research has shown that IFITM3 plays an important role in the tumorigenesis of many malignancies. We investigated the clinicopathological variables and prognostic value of IFITM3 in stage IIA esophageal squamous cell carcinoma (ESCC) patients. METHODS: Immunohistochemistry and Western blot analysis were used to examine IFITM3 expression in tumor specimens. The relationships between IFITM3 expression and clinicopathological variables, as well as the five-year survival and recurrence status of patients, were analyzed...
November 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28842783/population-genetics-of-ifitm3-in-portugal-and-central-africa-reveals-a-potential-modifier-of-influenza-severity
#14
Susana David, Vanessa Correia, Liliana Antunes, Ricardo Faria, José Ferrão, Paula Faustino, Baltazar Nunes, Fernando Maltez, João Lavinha, Helena Rebelo de Andrade
Influenza epidemics are a serious global public health and economic problem. The IFITM3 allele (rs12252-C) was suggested as a population-based genetic risk factor for severe influenza virus infection by A(H1N1)pdm09. We analyzed the population genetics of IFITM3 variants in the Portuguese general population (n = 200) and Central Africans (largely Angolan) (n = 148) as well as its association to influenza severity in Portuguese patients (n = 41). Seven SNPs, within the 352 bp IFITM3 amplicon around rs12252, were identified...
August 25, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28835547/ifitm3-requires-an-amphipathic-helix-for-antiviral-activity
#15
Nicholas M Chesarino, Alex A Compton, Temet M McMichael, Adam D Kenney, Lizhi Zhang, Victoria Soewarna, Matthew Davis, Olivier Schwartz, Jacob S Yount
Interferon-induced transmembrane protein 3 (IFITM3) is a cellular factor that blocks virus fusion with cell membranes. IFITM3 has been suggested to alter membrane curvature and fluidity, though its exact mechanism of action is unclear. Using a bioinformatic approach, we predict IFITM3 secondary structures and identify a highly conserved, short amphipathic helix within a hydrophobic region of IFITM3 previously thought to be a transmembrane domain. Consistent with the known ability of amphipathic helices to alter membrane properties, we show that this helix and its amphipathicity are required for the IFITM3-dependent inhibition of influenza virus, Zika virus, vesicular stomatitis virus, Ebola virus, and human immunodeficiency virus infections...
October 2017: EMBO Reports
https://www.readbyqxmd.com/read/28834009/chemical-synthesis-of-the-highly-hydrophobic-antiviral-membrane-associated-protein-ifitm3-and-modified-variants
#16
Thibault J Harmand, Vijaya R Pattabiraman, Jeffrey W Bode
Interferon-induced transmembrane protein 3 (IFITM3) is an antiviral transmembrane protein that is thought to serve as the primary factor for inhibiting the replication of a large number of viruses, including West Nile virus, Dengue virus, Ebola virus, and Zika virus. Production of this 14.5 kDa, 133-residue transmembrane protein, especially with essential posttranslational modifications, by recombinant expression is challenging. In this report, we document the chemical synthesis of IFTIM3 in multi-milligram quantities (>15 mg) and the preparation of phosphorylated and fluorescent variants...
October 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28815942/plasma-membrane-protein-profiling-in-beta-amyloid-treated-microglia-cell-line
#17
Virginia Correani, Laura Di Francesco, Giuseppina Mignogna, Cinzia Fabrizi, Stefano Leone, Alessandra Giorgi, Alessia Passeri, Roberto Casata, Lorenzo Fumagalli, Bruno Maras, M Eugenia Schininà
In the responsiveness of microglia to toxic stimuli, plasma membrane proteins play a key role. In this study we treated with a synthetic beta amyloid peptide murine microglial cells metabolically differently labelled with stable isotope amino acids (SILAC). The plasma membrane was selectively enriched by a multi-stage aqueous two-phase partition system. We were able to identify by 1D-LC-MS/MS analyses 1577 proteins, most of them are plasma membrane proteins according to the Gene Ontology annotation. An unchanged level of amyloid receptors in this data set suggests that microglia preserve their responsiveness capability to the environment even after 24-h challenge with amyloid peptides...
September 2017: Proteomics
https://www.readbyqxmd.com/read/28813716/no-correlation-of-the-disease-severity-of-influenza-a-virus-infection-with-the-rs12252-polymorphism-of-the-interferon-induced-transmembrane-protein-3-gene
#18
Yong-Chan Kim, Byung-Hoon Jeong
The 2009 H1N1 influenza pandemic, which involved a more pathogenic virus than seasonal influenza viruses, rapidly spread around the world and caused many deaths in humans. The members of the interferon-induced transmembrane (IFITM) protein family prevent viral replication and are crucial for defending the host cell against influenza A virus (IAV). Several studies suggest that the CC genotype at the single nucleotide polymorphism (SNP) rs12252 of IFITM3 confers a genetic predisposition to pandemic influenza A in Europeans and Han Chinese, although one study in a British cohort failed to show an association...
2017: Intervirology
https://www.readbyqxmd.com/read/28714988/snp-mediated-disruption-of-ctcf-binding-at-the-ifitm3-promoter-is-associated-with-risk-of-severe-influenza-in-humans
#19
E Kaitlynn Allen, Adrienne G Randolph, Tushar Bhangale, Pranay Dogra, Maikke Ohlson, Christine M Oshansky, Anthony E Zamora, John P Shannon, David Finkelstein, Amy Dressen, John DeVincenzo, Miguela Caniza, Ben Youngblood, Carrie M Rosenberger, Paul G Thomas
Previous studies have reported associations of IFITM3 SNP rs12252 with severe influenza, but evidence of association and the mechanism by which risk is conferred remain controversial. We prioritized SNPs in IFITM3 on the basis of putative biological function and identified rs34481144 in the 5' UTR. We found evidence of a new association of rs34481144 with severe influenza in three influenza-infected cohorts characterized by different levels of influenza illness severity. We determined a role for rs34481144 as an expression quantitative trait locus (eQTL) for IFITM3, with the risk allele associated with lower mRNA expression...
August 2017: Nature Medicine
https://www.readbyqxmd.com/read/28713779/ifitm3-rs12252-c-variant-increases-potential-risk-for-severe-influenza-virus-infection-in-chinese-population
#20
Yang Pan, Peng Yang, Tao Dong, Yi Zhang, Weixian Shi, Xiaomin Peng, Shujuan Cui, Daitao Zhang, Guilan Lu, Yimeng Liu, Shuangsheng Wu, Quanyi Wang
Background: Interferon Inducible Transmembrane 3 (IFITM3) is a key factor in interferon pathway and it involves host's immune response against multiple viruses. IFITM3 rs12252-C was associated with severe influenza virus infection in several studies, however whether this association is universal to all types of influenza virus or diverse ethnic populations remain controversial. Method: A case-control genetic association study was performed from September 2013 to April 2014 and September 2014 to April 2015. All samples were tested for influenza using RT-PCR, and genotyped by High Resolution Melting assay...
2017: Frontiers in Cellular and Infection Microbiology
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