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IFITM3

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https://www.readbyqxmd.com/read/28314479/new-insights-into-the-effects-and-mechanism-of-a-classic-traditional-chinese-medicinal-formula-on-influenza-prevention
#1
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
#2
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
#3
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...
February 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28213474/a-bayesian-approach-for-analysis-of-whole-genome-bisulphite-sequencing-data-identifies-disease-associated-changes-in-dna-methylation
#4
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 bisulphite 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 whilst taking into account the distance between CpG sites as a covariate...
February 17, 2017: Genetics
https://www.readbyqxmd.com/read/28100616/the-v3-loop-of-hiv-1-env-determines-viral-susceptibility-to-ifitm3-impairment-of-viral-infectivity
#5
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
#6
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...
January 3, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28040064/klf5-is-involved-in-regulation-of-ifitm1-2-and-3-genes-during-h5n1-virus-infection-in-a549-cells
#7
H-F Wang, L Chen, J Luo, H-X He
The interferon-induced transmembrane (IFITM) proteins usually protect cells from many virus infections by viral entry and replication. Thus, the present study aimed to identification novel regulation factors of IFITM genes. Our data showed up-regulation of IFITM1, IFITM2, and IFITM3 genes in A549 by H5N1 virus infection. However, IFITM1 was not affected, IFITM2 and IFITM3 increases expression following different concentration H5N1 virus infection in HEK293T cells. This is the first time to find differences of IFITM1 transcription in different cells with the H5N1 virus infection...
November 30, 2016: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/27882230/evaluation-of-interferon-induced-transmembrane-protein-3-ifitm3-rs7478728-and-rs3888188-polymorphisms-and-the-risk-of-pulmonary-tuberculosis
#8
Mohammad Naderi, Mohammad Hashemi, Fatemeh Abedipour, Gholamreza Bahari, Maryam Rezaei, Mohsen Taheri
The current study aimed to examine the possible association between the interferon-induced transmembrane protein-3 (IFITM3) gene polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample population. This case-control study was conducted on 188 PTB patients and 169 healthy subjects. The rs7478728 and rs3888188 variants of IFITM3 were genotyped using polymerase chain reaction-restriction fragment length polymorphism. The findings showed no significant association between rs7478728 polymorphism and risk of PTB...
November 2016: Biomedical Reports
https://www.readbyqxmd.com/read/27835870/no-role-of-ifitm3-in-brain-tumor-formation-in-vivo
#9
Nevenka Dudvarski Stankovic, Nicola Hoppmann, Marcin Teodorczyk, Ella L Kim, Matthias Bros, Alf Giese, Frauke Zipp, Mirko H H Schmidt
Glioblastoma multiforme (GBM) is one of the most lethal solid tumors in adults. Despite aggressive treatment approaches for patients, GBM recurrence is inevitable, in part due to the existence of stem-like brain tumor-propagating cells (BTPCs), which produce factors rendering them resistant to radio- and chemotherapy. Comparative transcriptome analysis of irradiated, patient-derived BTPCs revealed a significant upregulation of the interferon-inducible transmembrane protein 3 (IFITM3), suggesting the protein as a factor mediating radio resistance...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27783949/solute-carrier-ntcp-regulates-innate-antiviral-immune-responses-targeting-hepatitis-c-virus-infection-of-hepatocytes
#10
Eloi R Verrier, Che C Colpitts, Charlotte Bach, Laura Heydmann, Laetitia Zona, Fei Xiao, Christine Thumann, Emilie Crouchet, Raphaël Gaudin, Camille Sureau, François-Loïc Cosset, Jane A McKeating, Patrick Pessaux, Yujin Hoshida, Catherine Schuster, Mirjam B Zeisel, Thomas F Baumert
Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs), including IFITM3...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27768298/site-specific-bioorthogonal-labeling-for-fluorescence-imaging-of-intracellular-proteins-in-living-cells
#11
Tao Peng, Howard C Hang
Over the past years, fluorescent proteins (e.g., green fluorescent proteins) have been widely utilized to visualize recombinant protein expression and localization in live cells. Although powerful, fluorescent protein tags are limited by their relatively large sizes and potential perturbation to protein function. Alternatively, site-specific labeling of proteins with small-molecule organic fluorophores using bioorthogonal chemistry may provide a more precise and less perturbing method. This approach involves site-specific incorporation of unnatural amino acids (UAAs) into proteins via genetic code expansion, followed by bioorthogonal chemical labeling with small organic fluorophores in living cells...
November 2, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27720938/identification-of-gene-expression-profiling-associated-with-erlotinib-related-skin-toxicity-in-pancreatic-adenocarcinoma-patients
#12
Octavio Caba, Antonio Irigoyen, Cristina Jimenez-Luna, Manuel Benavides, Francisco M Ortuño, Javier Gallego, Ignacio Rojas, Carmen Guillen-Ponce, Carolina Torres, Enrique Aranda, Jose Prados
Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that showed activity against pancreatic ductal adenocarcinoma (PDAC). The drug's most frequently reported side effect as a result of EGFR inhibition is skin rash (SR), a symptom which has been associated with a better therapeutic response to the drug. Gene expression profiling can be used as a tool to predict which patients will develop this important cutaneous manifestation. The aim of the present study was to identify which genes may influence the appearance of SR in PDAC patients...
October 6, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27707929/constitutively-expressed-ifitm3-protein-in-human-endothelial-cells-poses-an-early-infection-block-to-human-influenza-viruses
#13
Xiangjie Sun, Hui Zeng, Amrita Kumar, Jessica A Belser, Taronna R Maines, Terrence M Tumpey
A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses...
December 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27667301/identification-of-differentially-expressed-transcripts-targeted-by-the-knockdown-of-endogenous-ifitm3
#14
Chen Shen, Ying-Jia Li, Qing-Qin Yin, Wei-Wei Jiao, Qin-Jing Li, Jing Xiao, Lin Sun, Fang Xu, Jie-Qiong Li, Hui Qi, A-Dong Shen
Interferon inducible transmembrane protein 3 (IFITM3) is a double transmembrane protein. As a member of the IFITM family, IFITM3 can be upregulated by interferon (IFN) to be involved in various biological processes. In order to determine whether gene expression profiles can be altered by a lack of IFITM3, the present study used shRNAs lentivirus for knocking down the endogenous expression of IFITM3 in human HeLa cells and human whole genome microarrays to obtain gene expression profiles. A total of 1,011 downregulated transcripts and 615 upregulated transcripts were identified using the Agilent expression platform...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27640936/resistance-of-transmitted-founder-hiv-1-to-ifitm-mediated-restriction
#15
Toshana L Foster, Harry Wilson, Shilpa S Iyer, Karen Coss, Katie Doores, Sarah Smith, Paul Kellam, Andrés Finzi, Persephone Borrow, Beatrice H Hahn, Stuart J D Neil
Interferon-induced transmembrane proteins (IFITMs) restrict the entry of diverse enveloped viruses through incompletely understood mechanisms. While IFITMs are reported to inhibit HIV-1, their in vivo relevance is unclear. We show that IFITM sensitivity of HIV-1 strains is determined by the co-receptor usage of the viral envelope glycoproteins as well as IFITM subcellular localization within the target cell. Importantly, we find that transmitted founder HIV-1, which establishes de novo infections, is uniquely resistant to the antiviral activity of IFITMs...
October 12, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27601221/natural-mutations-in-ifitm3-modulate-post-translational-regulation-and-toggle-antiviral-specificity
#16
Alex A Compton, Nicolas Roy, Françoise Porrot, Anne Billet, Nicoletta Casartelli, Jacob S Yount, Chen Liang, Olivier Schwartz
The interferon-induced transmembrane (IFITM) proteins protect host cells from diverse virus infections. IFITM proteins also incorporate into HIV-1 virions and inhibit virus fusion and cell-to-cell spread, with IFITM3 showing the greatest potency. Here, we report that amino-terminal mutants of IFITM3 preventing ubiquitination and endocytosis are more abundantly incorporated into virions and exhibit enhanced inhibition of HIV-1 fusion. An analysis of primate genomes revealed that IFITM3 is the most ancient antiviral family member of the IFITM locus and has undergone a repeated duplication in independent host lineages...
November 2016: EMBO Reports
https://www.readbyqxmd.com/read/27557587/isolation-of-mammalian-oogonial-stem-cells-by-antibody-based-fluorescence-activated-cell-sorting
#17
Deanna M Navaroli, Jonathan L Tilly, Dori C Woods
The ability to isolate and subsequently culture mitotically active female germ cells from adult ovaries, referred to as either oogonial stem cells (OSCs) or adult female germline stem cells (aFGSCs), has provided a robust system to study female germ cell development under multiple experimental conditions, and in many species. Flow cytometry or fluorescence-activated cell sorting (FACS) is an integral part of many isolation and characterization protocols. Here, we provide methodological details for antibody-based flow cytometric isolation of OSCs using antibodies specific for external epitopes of the proteins Ddx4 or Ifitm3, alone or in combination with the use of fluorescent reporter mice...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27542257/dynamics-of-pbmc-gene-expression-in-hepatitis-c-virus-genotype-1-infected-patients-during-combined-peginterferon-ribavirin-therapy
#18
Ming-Ying Lu, Ching-I Huang, Ming-Yen Hsieh, Tusty-Juan Hsieh, Edward Hsi, Pei-Chien Tsai, Yi-Shan Tsai, Ching-Chih Lin, Meng-Hsuan Hsieh, Po-Cheng Liang, Yi-Hung Lin, Nai-Jen Hou, Ming-Lun Yeh, Chung-Feng Huang, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs), which can produce interferon to defend against virus infection. We hypothesized that dynamic gene expression in PBMCs might impact the treatment efficacy of peginterferon/ribavirin in HCV patients. PBMCs were collected at baseline, 1st week and 4th week of treatment from 27 chronic HCV-1 patients with 48-week peginterferon/ribavirin therapy (screening dataset n = 7; validation dataset n = 20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after end-of-treatment...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27492307/ifitm3-and-severe-influenza-virus-infection-no-evidence-of-genetic-association
#19
M López-Rodríguez, E Herrera-Ramos, J Solé-Violán, J J Ruíz-Hernández, L Borderías, J P Horcajada, E Lerma-Chippirraz, O Rajas, M Briones, M C Pérez-González, M A García-Bello, E López-Granados, F Rodriguez de Castro, C Rodríguez-Gallego
Influenza virus infection (IVI) is typically subclinical or causes a self-limiting upper respiratory disease. However, in a small subset of patients IVI rapidly progresses to primary viral pneumonia (PVP) with respiratory failure; a minority of patients require intensive care unit admission. Inherited and acquired variability in host immune responses may influence susceptibility and outcome of IVI. However, the molecular basis of such human factors remains largely elusive. It has been proposed that homozygosity for IFITM3 rs12252-C is associated with a population-attributable risk of 5...
November 2016: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/27440901/the-interferon-stimulated-gene-ifitm3-restricts-infection-and-pathogenesis-of-arthritogenic-and-encephalitic-alphaviruses
#20
Subhajit Poddar, Jennifer L Hyde, Matthew J Gorman, Michael Farzan, Michael S Diamond
UNLABELLED: Host cells respond to viral infections by producing type I interferon (IFN), which induces the expression of hundreds of interferon-stimulated genes (ISGs). Although ISGs mediate a protective state against many pathogens, the antiviral functions of the majority of these genes have not been identified. IFITM3 is a small transmembrane ISG that restricts a broad range of viruses, including orthomyxoviruses, flaviviruses, filoviruses, and coronaviruses. Here, we show that alphavirus infection is increased in Ifitm3(-/-) and Ifitm locus deletion (Ifitm-del) fibroblasts and, reciprocally, reduced in fibroblasts transcomplemented with Ifitm3...
October 1, 2016: Journal of Virology
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