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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
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...
October 21, 2016: Journal of the American Chemical Society
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
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. Here, 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...
October 5, 2016: Journal of Virology
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...
September 26, 2016: Molecular Medicine Reports
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
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...
September 6, 2016: EMBO Reports
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
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...
August 17, 2016: Oncotarget
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
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
X-M Zhao, L-S Cui, H-S Hao, H-Y Wang, S-J Zhao, W-H Du, D Wang, Y Liu, H-B Zhu
Research on bovine embryonic stem cells (bESCs) has been hampered because bESCs are cultured in conditions that are based on information obtained from culturing mouse and human inner cell mass (ICM) cells. The aim of this study was to compare gene expression in ICM and trophectoderm (TE) cell lineages of bovine embryos and to discuss the findings relative to information available for mice and humans. We separated a high-purity (>90%) ICM and TE from bovine blastocysts by magnetic-activated cell sorting and analysed their transcriptomes by single cell RNA-seq...
October 2016: Reproduction in Domestic Animals, Zuchthygiene
Matthew J Gorman, Subhajit Poddar, Michael Farzan, Michael S Diamond
UNLABELLED: The interferon-induced transmembrane protein (IFITM) family of proteins inhibit infection of several different enveloped viruses in cell culture by virtue of their ability to restrict entry and fusion from late endosomes. As few studies have evaluated the importance of Ifitm3 in vivo in restricting viral pathogenesis, we investigated its significance as an antiviral gene against West Nile virus (WNV), an encephalitic flavivirus, in cells and mice. Ifitm3(-/-) mice were more vulnerable to lethal WNV infection, and this was associated with greater virus accumulation in peripheral organs and central nervous system tissues...
September 15, 2016: Journal of Virology
Huawei Zhang, Haixue Zheng, Ping Qian, Jinfang Xu, Xi Yang, Rui Zhou, Huanchun Chen, Xiangmin Li
Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, and can cause severe economic loss. Interferon-induced transmembrane (IFITM) proteins constitute a family of viral restriction factors that can inhibit the replication of several types of viruses. Our previous study showed that overexpression of swine IFITM3 (sIFITM3) impeded replication of the FMD virus (FMDV) in BHK-21 cells and mice. In this study, sIFITM3-transgenic (TG) pigs were produced by handmade cloning. Results showed that sIFITM3 was highly overexpressed in many organs of sIFITM3-TG pigs compared to wild-type pigs...
August 15, 2016: Veterinary Microbiology
Vânia Gaio, Baltazar Nunes, Pedro Pechirra, Patrícia Conde, Raquel Guiomar, Carlos Matias Dias, Marta Barreto
BACKGROUND: Recent studies suggest an association between the Interferon Inducible Transmembrane 3 (IFITM3) rs12252 variant and the course of influenza infection. However, it is not clear whether the reported association relates to influenza infection severity. The aim of this study was to estimate the hospitalization risk associated with this variant in Influenza Like Illness (ILI) patients during the H1N1 pandemic influenza. METHODS: A case-control genetic association study was performed, using nasopharyngeal/oropharyngeal swabs collected during the H1N1 pandemic influenza...
2016: PloS One
George Savidis, Jill M Perreira, Jocelyn M Portmann, Paul Meraner, Zhiru Guo, Sharone Green, Abraham L Brass
Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses...
June 14, 2016: Cell Reports
Jordan Wilkins, Yi-Min Zheng, Jingyou Yu, Chen Liang, Shan-Lu Liu
Interferon-induced transmembrane (IFITM) proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs...
2016: PloS One
Stuart Weston, Stephanie Czieso, Ian J White, Sarah E Smith, Rachael S Wash, Carmen Diaz-Soria, Paul Kellam, Mark Marsh
Interferon inducible transmembrane proteins (IFITMs) are broad-spectrum antiviral factors. In cell culture the entry of many enveloped viruses, including orthomyxo-, flavi-, and filoviruses, is inhibited by IFITMs, though the mechanism(s) involved remain unclear and may vary between viruses. We demonstrate that Sindbis and Semliki Forest virus (SFV), which both use endocytosis and acid-induced membrane fusion in early endosomes to infect cells, are restricted by the early endosomal IFITM3. The late endosomal IFITM2 is less restrictive and the plasma membrane IFITM1 does not inhibit normal infection by either virus...
September 2016: Traffic
Romain Appourchaux, Andrea Cimarelli
No abstract text is available yet for this article.
April 2016: Médecine Sciences: M/S
Shunsuke Kidani, Yuya Okuzaki, Hidenori Kaneoka, Seiya Asai, Seitaro Murakami, Yusuke Murase, Shinji Iijima, Ken-Ichi Nishijima
In mammals, interferon-inducible transmembrane proteins (IFITMs) prevent infections by various enveloped viruses. The expression of IFITMs in chicken was herein examined in the adult and embryonic organs using a quantitative reverse-transcription-polymerase chain reaction. The results obtained revealed that IFITM3 was expressed at a higher level than IFITM1, 2 and 5, in both embryonic and adult organs. However, the expression levels of IFITMs in embryonic organs were less than 5 % of those in adult lungs. Among the embryonic tissues examined, primordial germ cells (PGCs) at day 2...
April 27, 2016: Cytotechnology
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