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IFITM3

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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
#1
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
#2
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...
August 30, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28630320/%C3%AE-20-ifitm2-differentially-restricts-x4-and-r5-hiv-1
#10
Wan-Lin Wu, Christopher Robert Grotefend, Ming-Ting Tsai, Yi-Ling Wang, Vladimir Radic, Hyungjin Eoh, I-Chueh Huang
CCR5 (R5)-tropic, but not CXCR4 (X4)-tropic, HIV-1 is associated with primary HIV-1 infection and transmission. Recent studies have shown that IFN-induced transmembrane (IFITM) proteins, including IFITM1, IFITM2, and IFITM3, restrict a broad range of viruses. Here, we demonstrate that an IFITM2 isoform (Δ20 IFITM2) lacking 20 amino acids at the N terminus differentially restricts X4 and R5 HIV-1. Δ20 IFITM2 suppresses replication of X4 HIV-1 strains by inhibiting their entry. High levels of Δ20 IFITM2 expression could be detected in CD4(+) T cells and in monocytes...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28550121/bcl6-represses-antiviral-resistance-in-follicular-t-helper-cells
#11
Tohti Amet, Young Min Son, Li Jiang, In Su Cheon, Su Huang, Samir K Gupta, Alexander L Dent, Luis J Montaner, Qigui Yu, Jie Sun
Follicular Th (Tfh) cells are a distinct subset of Th cells that help B cells produce class-switched antibodies. Studies have demonstrated that Tfh cells are highly prone to HIV infection and replication. However, the molecular mechanisms underlying this phenomenon are largely unclear. Here, we show that murine and human Tfh cells have diminished constitutive expression of IFN-stimulated genes (ISGs) inclusive of antiviral resistance factor MX dynamin-like GTPase 2 (MX2) and IFN-induced transmembrane 3 (IFITM3) compared with non-Tfh cells...
August 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28544512/interferon-induced-transmembrane-protein-3-regulates-the-growth-and-invasion-of-human-lung-adenocarcinoma
#12
Dong Zhang, Huimin Wang, Huijie He, Haiying Niu, Yu Li
BACKGROUND: Interferon induced transmembrane protein 3 (IFITM3) plays an important role in the tumorigenesis and progression of multiple cancers. This study investigated the expression and function of IFITM3 in human lung adenocarcinoma. METHODS: Fifty human lung adenocarcinoma tissues were collected. IFITM3 expression was assessed by immunohistochemical staining. The clinicopathologic characteristics of all patients were analyzed. RESULTS: IFITM3 was mainly detected in the cytoplasm of advanced cancer tissues and its expression was correlated with tumor malignancy grade...
July 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28531322/evaluation-of-ifitm3-rs12252-association-with-severe-pediatric-influenza-infection
#13
MULTICENTER STUDY
Adrienne G Randolph, Wai-Ki Yip, Emma Kaitlynn Allen, Carrie M Rosenberger, Anna A Agan, Stephanie A Ash, Yu Zhang, Tushar R Bhangale, David Finkelstein, Natalie Z Cvijanovich, Peter M Mourani, Mark W Hall, Helen C Su, Paul G Thomas
Background: Interferon-induced transmembrane protein 3 (IFITM3) restricts endocytic fusion of influenza virus. IFITM3 rs12252_C, a putative alternate splice site, has been associated with influenza severity in adults. IFITM3 has not been evaluated in pediatric influenza. Methods: The Pediatric Influenza (PICFLU) study enrolled children with suspected influenza infection across 38 pediatric intensive care units during November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing...
July 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28515008/localization-and-distribution-of-gonadal-proteins-in-the-oviparous-lizard-sceloporus-aeneus-squamata-phrynosomatidae
#14
Antonio-Rubio Nivia Rocio, Villagrán-SantaCruz Maricela, Moreno-Mendoza Norma
Among vertebrates, several specific proteins are involved in the function and development of gonads. Several genes such as SOX9, FOXL2, DDX4, IFITM3, and DPPA3, are active during embryonic differentiation and maintain their expression in adult tissues, playing important roles in the function and development of the line cell, where these are produced. Among reptiles, molecular mechanisms for sex differentiation have been analyzed in turtles, crocodiles, and some lizards, while in adult stages such studies are scarce...
June 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28511927/coordinated-regulation-of-ifitm1-2-and-3-genes-by-an-ifn-responsive-enhancer-through-long-range-chromatin-interactions
#15
Ping Li, Ming-Lei Shi, Wen-Long Shen, Zhang Zhang, De-Jian Xie, Xiang-Yuan Zhang, Chao He, Yan Zhang, Zhi-Hu Zhao
Interferon-induced transmembrane protein (IFITM) 1, 2 and 3 genes encode a family of interferon (IFN)-induced transmembrane proteins that block entry of a broad spectrum of pathogens. However, the transcriptional regulation of these genes, especially whether there exist any enhancers and their roles during the IFN induction process remain elusive. Here, through public data mining, episomal luciferase reporter assay and in vivo CRISPR-Cas9 genome editing, we identified an IFN-responsive enhancer located 35kb upstream of IFITM3 gene promoter upregulating the IFN-induced expression of IFITM1, 2 and 3 genes...
August 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28510725/ifitm3-tlr3-and-cd55-gene-snps-and-cumulative-genetic-risks-for-severe-outcomes-in-chinese-patients-with-h7n9-h1n1pdm09-influenza
#16
Nelson Lee, Bin Cao, Changwen Ke, Hongzhou Lu, Yunwen Hu, Claudia Ha Ting Tam, Ronald Ching Wan Ma, Dawei Guan, Zhaoqin Zhu, Hui Li, Mulei Lin, Rity Y K Wong, Irene M H Yung, Tin-Nok Hung, Kirsty Kwok, Peter Horby, David Shu Cheong Hui, Martin Chi Wai Chan, Paul Kay Sheung Chan
Background: We examined associations between single-nucleotide polymorphisms (SNPs) of IFITM3, TLR3, and CD55 genes and influenza clinical outcomes in Chinese. Methods: A multicenter study was conducted on 275 adult cases of avian (H7N9) and pandemic (H1N1pdm09) influenza. Host DNA was extracted from diagnostic respiratory samples; IFITM3 rs12252, TLR3 rs5743313, CD55 rs2564978, and TLR4 rs4986790/4986791 were targeted for genotyping (Sanger sequencing). The primary outcome analyzed was death...
July 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28473814/avian-interferon-inducible-transmembrane-protein-family-effectively-restricts-avian-tembusu-virus-infection
#17
Shilong Chen, Long Wang, Jieying Chen, Lanlan Zhang, Song Wang, Mohsan U Goraya, Xiaojuan Chi, Yang Na, Wenhan Shao, Zhou Yang, Xiancheng Zeng, Shaoying Chen, Ji-Long Chen
Avian Tembusu virus (ATMUV) is a highly pathogenic flavivirus that causes significant economic losses to the Chinese poultry industry. Our previous experiments demonstrated that ATMUV infection effectively triggered host innate immune response through MDA5 and TLR3-dependent signaling pathways. However, little information is available on the role of interferon-stimulated genes (ISGs) in defending against ATMUV infection. In this study, we found that ATMUV infection induced robust expression of type I and type III interferon (IFNs) in duck tissues...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28473450/zika-virus-induces-massive-cytoplasmic-vacuolization-and-paraptosis-like-death-in-infected-cells
#18
Blandine Monel, Alex A Compton, Timothée Bruel, Sonia Amraoui, Julien Burlaud-Gaillard, Nicolas Roy, Florence Guivel-Benhassine, Françoise Porrot, Pierre Génin, Laurent Meertens, Laura Sinigaglia, Nolwenn Jouvenet, Robert Weil, Nicoletta Casartelli, Caroline Demangel, Etienne Simon-Lorière, Arnaud Moris, Philippe Roingeard, Ali Amara, Olivier Schwartz
The cytopathic effects of Zika virus (ZIKV) are poorly characterized. Innate immunity controls ZIKV infection and disease in most infected patients through mechanisms that remain to be understood. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interferon-induced transmembrane proteins (IFITM), a family of broad-spectrum antiviral factors, during viral replication. We report that ZIKV induces massive vacuolization followed by "implosive" cell death in human epithelial cells, primary skin fibroblasts and astrocytes, a phenomenon which is exacerbated when IFITM3 levels are low...
June 14, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28435159/ifitm3-inhibits-virus-triggered-induction-of-type-i-interferon-by-mediating-autophagosome-dependent-degradation-of-irf3
#19
Li-Qun Jiang, Tian Xia, Yun-Hong Hu, Ming-Shun Sun, Shuang Yan, Cao-Qi Lei, Hong-Bing Shu, Ji-Hua Guo, Yu Liu
Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that can be induced by viral infection and interferons (IFNs). It inhibits the entry and replication of many viruses, which are independent of receptor usage but dependent on processes that occur in endosomes. In this study, we demonstrate that IFITM3 plays important roles in regulating the RNA-virus-triggered production of IFN-β in a negative-feedback manner. Overexpression of IFITM3 inhibited Sendai virus-triggered induction of IFN-β, whereas knockdown of IFITM3 had the opposite effect...
April 24, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28435158/a-balancing-act-between-ifitm3-and-irf3
#20
Temet M McMichael, Mahesh Chemudupati, Jacob S Yount
No abstract text is available yet for this article.
April 24, 2017: Cellular & Molecular Immunology
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