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IFITM3

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https://www.readbyqxmd.com/read/28630320/%C3%AE-20-ifitm2-differentially-restricts-x4-and-r5-hiv-1
#1
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...
June 19, 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
#2
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...
May 26, 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
#3
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...
May 23, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28531322/evaluation-of-ifitm3-rs12252-association-with-severe-pediatric-influenza-infection
#4
Adrienne G Randolph, Wai-Ki Yip, E Kaitlyn Allen, Carrie M Rosenberger, Anna A Agan, Stephanie A Ash, Yu Zhang, Tushar R Bhangale, David Finkelstein, Natalie Cvijanovich, Peter M Mourani, Mark Hall, Helen C Su, Paul G Thomas
Background: Interferon inducible 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 PICFLU Study enrolled children with suspected influenza infection across 38 pediatric intensive care units November 2008 to April 2016. IFITM3 was sequenced in patients and parents were genotyped for specific variants for family-based association testing...
May 20, 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
#5
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...
May 14, 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
#6
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 are 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 exists any enhancers and their roles during the IFN induction process remain elusive. Here, combining episomal luciferase reporter assay and in vivo genome editing, we identified an IFNβ-responsive enhancer located 35kb upstream of IFITM3 gene promoter upregulating the IFNβ-induced expression of IFITM1, 2 and 3 genes, thus contributing to IFNβ-mediated resistance to influenza A virus (IAV) infection...
May 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28510725/ifitm3-tlr3-and-cd55-genes-snps-and-cumulative-ge-netic-risks-for-severe-outcomes-in-chinese-patients-with-h7n9-h1n1pdm09-influenza
#7
Nelson Lee, Bin Cao, Changwen Ke, Hongzhou Lu, Yunwen Hu, Ht Claudia Tam, Cw Ronald Ma, Dawei Guan, Zhaoqin Zhu, Hui Li, Lin Mulei, Rity Yk Wong, Irene Mh Yung, Tin-Nok Hung, Kirsty Kwok, Peter Horby, Sc David Hui, Cw Martin Chan, Ks Paul Chan
Background: We examined associations between SNPs (single-nucleotide-polymorphisms) of IFITM3, TLR3, and CD55 genes and influenza clinical outcomes in Chinese patients. Methods: A multicenter-study was conducted on 275 adult cases of prospectively-diagnosed H7N9 and H1N1pdm09 infections. Host DNA was extracted from diagnostic respiratory samples; IFITM3 rs12252, TLR3 rs5743313, CD55 rs2564978, and TLR4 rs4986790/4986791 were targeted for genotyping by Sanger-sequencing...
May 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28473814/avian-interferon-inducible-transmembrane-protein-family-effectively-restricts-avian-tembusu-virus-infection
#8
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
#9
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
#10
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
#11
Temet M McMichael, Mahesh Chemudupati, Jacob S Yount
No abstract text is available yet for this article.
April 24, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28386554/identification-of-ifitm1-and-ifitm3-in-goose-gene-structure-expression-patterns-and-immune-reponses-against-tembusu-virus-infection
#12
Anqi Wang, Lipei Sun, Mingshu Wang, Renyong Jia, Dekang Zhu, Mafeng Liu, Kunfeng Sun, Qiao Yang, Ying Wu, Xiaoyue Chen, Anchun Cheng, Shun Chen
As interferon-stimulated genes (ISGs), interferon-inducible transmembrane proteins 1 and 3 (IFITM1 and IFITM3) can effectively inhibit the replication of multiple viruses. Here, goose IFITM1 and IFITM3 were cloned and identified for the first time. The two proteins share the same topological structure and several important sites critical for the antiviral functions in other species are conserved in the goose. Goose IFITM1 and IFITM3 are most closely related to their respective orthologs in ducks; these proteins exhibited high mRNA transcript levels in immune-related tissues, including the thymus, bursa of Fabricius, and Harderian gland, compared to other tissues...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28362576/ambra1-spatially-regulates-src-activity-and-src-fak-mediated-cancer-cell-invasion-via-trafficking-networks
#13
Christina Schoenherr, Adam Byron, Emma Sandilands, Ketevan Paliashvili, George S Baillie, Amaya Garcia-Munoz, Cristina Valacca, Francesco Cecconi, Bryan Serrels, Margaret C Frame
Here, using mouse squamous cell carcinoma cells, we report a completely new function for the autophagy protein Ambra1 as the first described 'spatial rheostat' controlling the Src/FAK pathway. Ambra1 regulates the targeting of active phospho-Src away from focal adhesions into autophagic structures that cancer cells use to survive adhesion stress. Ambra1 binds to both FAK and Src in cancer cells. When FAK is present, Ambra1 is recruited to focal adhesions, promoting FAK-regulated cancer cell direction-sensing and invasion...
March 31, 2017: ELife
https://www.readbyqxmd.com/read/28356532/ph-optimum-of-hemagglutinin-mediated-membrane-fusion-determines-sensitivity-of-influenza-a-viruses-to-the-interferon-induced-antiviral-state-and-ifitms
#14
Thomas Gerlach, Luca Hensen, Tatyana Matrosovich, Janina Bergmann, Michael Winkler, Christin Peteranderl, Hans-Dieter Klenk, Friedemann Weber, Susanne Herold, Stefan Pöhlmann, Mikhail Matrosovich
The replication and pathogenicity of influenza A viruses (IAVs) critically depend on their ability to tolerate the antiviral interferon (IFN) response. To determine a potential role for the IAV hemagglutinin (HA) in viral sensitivity to IFN, we studied the restriction of IAV infection in IFN-β-treated human epithelial cells by using 2:6 recombinant IAVs that shared six gene segments of A/Puerto Rico/8/1934 virus (PR8) and contained HAs and neuraminidases of representative avian, human, and zoonotic H5N1 and H7N9 viruses...
June 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28314479/new-insights-into-the-effects-and-mechanism-of-a-classic-traditional-chinese-medicinal-formula-on-influenza-prevention
#15
Huan Chen, Chong Jie, Lu-Ping Tang, He Meng, Xiao-Bo Li, Yan-Bing Li, Le-Xing Chen, Chang Yan, Hiroshi Kurihara, Yi-Fang Li, Rong-Rong He
BACKGROUND: KangBingDu (KBD) is a classic traditional Chinese medicinal formula widely used to treat influenza. However, little information is available from controlled studies regarding the anti-influenza pharmacological activities of KBD and its underlying mechanisms, at least partly due to the lack of appropriate study models. PURPOSE: We hypothesized that KBD might provide a protection against influenza infection by reducing the host's susceptibility to viruses...
April 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28257482/rhesus-macaque-ifitm3-gene-polymorphisms-and-siv-infection
#16
Michael Winkler, Sabine Gärtner, Florian Wrensch, Michael Krawczak, Ulrike Sauermann, Stefan Pöhlmann
Interferon-induced transmembrane proteins (IFITMs) have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection, respectively. Rhesus macaques (Macaca mulatta) are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV) is one of the best models for HIV/AIDS in humans...
2017: PloS One
https://www.readbyqxmd.com/read/28240600/the-antiviral-restriction-factor-ifn-induced-transmembrane-protein-3-prevents-cytokine-driven-cmv-pathogenesis
#17
Maria A Stacey, Simon Clare, Mathew Clement, Morgan Marsden, Juneid Abdul-Karim, Leanne Kane, Katherine Harcourt, Cordelia Brandt, Ceri A Fielding, Sarah E Smith, Rachael S Wash, Silvia Gimeno Brias, Gabrielle Stack, George Notley, Emma L Cambridge, Christopher Isherwood, Anneliese O Speak, Zoë Johnson, Walter Ferlin, Simon A Jones, Paul Kellam, Ian R Humphreys
The antiviral restriction factor IFN-induced transmembrane protein 3 (IFITM3) inhibits cell entry of a number of viruses, and genetic diversity within IFITM3 determines susceptibility to viral disease in humans. Here, we used the murine CMV (MCMV) model of infection to determine that IFITM3 limits herpesvirus-associated pathogenesis without directly preventing virus replication. Instead, IFITM3 promoted antiviral cellular immunity through the restriction of virus-induced lymphopenia, apoptosis-independent NK cell death, and loss of T cells...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28213474/a-bayesian-approach-for-analysis-of-whole-genome-bisulfite-sequencing-data-identifies-disease-associated-changes-in-dna-methylation
#18
Owen J L Rackham, Sarah R Langley, Thomas Oates, Eleni Vradi, Nathan Harmston, Prashant K Srivastava, Jacques Behmoaras, Petros Dellaportas, Leonardo Bottolo, Enrico Petretto
DNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulfite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures in CpG methylation levels across the genome while taking into account the distance between CpG sites as a covariate...
April 2017: Genetics
https://www.readbyqxmd.com/read/28100616/the-v3-loop-of-hiv-1-env-determines-viral-susceptibility-to-ifitm3-impairment-of-viral-infectivity
#19
Yimeng Wang, Qinghua Pan, Shilei Ding, Zhen Wang, Jingyou Yu, Andrés Finzi, Shan-Lu Liu, Chen Liang
Interferon-inducible transmembrane proteins (IFITMs) inhibit a broad spectrum of viruses, including HIV-1. IFITM proteins deter HIV-1 entry when expressed in target cells and also impair HIV-1 infectivity when expressed in virus producer cells. However, little is known about how viruses resist IFITM inhibition. In this study, we have investigated the susceptibilities of different primary isolates of HIV-1 to the inhibition of viral infectivity by IFITMs. Our results demonstrate that the infectivity of different HIV-1 primary isolates, including transmitted founder viruses, is diminished by IFITM3 to various levels, with strain AD8-1 exhibiting strong resistance...
April 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28045025/interferon-epsilon-promotes-hiv-restriction-at-multiple-steps-of-viral-replication
#20
Albert Garcia-Minambres, Sahar G Eid, Niamh E Mangan, Corinna Pade, San S Lim, Antony Y Matthews, Nicole A de Weerd, Paul J Hertzog, Johnson Mak
Interferon epsilon (IFNɛ) is a type I IFN that is expressed constitutively in the female reproductive tract (FRT), and contributes to protection in models of sexually transmitted infections. Using multiple cell systems, including reporter cell lines and activated peripheral blood lymphocytes (PBLs), we show that recombinant IFNɛ impairs HIV infection at stage(s) post HIV entry and up to the translation of viral proteins. Consistent with this, IFNɛ upregulated a number of host cell restriction factors that block HIV at these stages of the replication cycle...
May 2017: Immunology and Cell Biology
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