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Encephalomyocarditis Virus Viroporin 2B Activates NLRP3 Inflammasome
Encephalomyocarditis Virus Viroporin 2B Activates NLRP3 Inflammasome Minako Ito, Yusuke Yanagi, Takeshi Ichinohe* Department of Virology, Faculty of Medicine, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan Abstract Nod-like receptors (NLRs) comprise a large family of intracellular pattern- recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed the inflammasomes. The NLR family, pyrin domain-containing 3 (NLRP3) is triggered by a diverse set of molecules and signals, and forms the NLRP3 inflammasome. Recent studies have indicated that both DNA and RNA viruses stimulate the NLRP3 inflammasome, leading to the secretion of interleukin 1 beta (IL-1b) and IL-18 following the activation of caspase-1. We previously demonstrated that the proton-selective ion channel M2 protein of influenza virus activates the NLRP3 inflammasome. However, the precise mechanism by which NLRP3 recognizes viral infections remains to be defined. Here, we demonstrate that encephalomyocarditis virus (EMCV), a positive strand RNA virus of the family Picornaviridae, activates the NLRP3 inflammasome in mouse dendritic cells and macrophages. Although transfection with RNA from EMCV virions or EMCV-infected cells induced robust expression of type I interferons in macrophages, it failed to stimulate secretion of IL-1b. Instead, the EMCV viroporin 2B was sufficient to cause inflammasome activation in lipopolysaccharide-primed macrophages. While cells untransfected or transfected with the gene encoding the EMCV non-structural protein 2A or 2C expressed NLRP3 uniformly throughout the cytoplasm, NLRP3 was redistributed to the perinuclear space in cells transfected with the gene encoding the EMCV 2B or influenza virus M2 protein. 2B proteins of other picornaviruses, poliovirus and enterovirus 71, also caused the NLRP3 redistribution. -
Global Burden of Norovirus and Prospects for Vaccine Development
Global Burden of Norovirus and Prospects for Vaccine Development Primary author Ben Lopman Centers for Disease Control and Prevention Contributors and Reviewers Robert Atmar, Baylor College of Medicine Ralph Baric, University of North Carolina Mary Estes, Baylor College of Medicine Kim Green, NIH; National Institute of Allergy and Infectious Diseases Roger Glass, NIH; Fogarty International Center Aron Hall, Centers for Disease Control and Prevention Miren Iturriza-Gómara, University of Liverpool Cherry Kang, Christian Medical College Bruce Lee, Johns Hopkins University Umesh Parashar, Centers for Disease Control and Prevention Mark Riddle, Naval Medical Research Center Jan Vinjé, Centers for Disease Control and Prevention The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, or the US Department of Health and Human Services. This work was funded in part by a grant from the Bill & Melinda Gates Foundation to the CDC Foundation. GLOBAL BURDEN OF NOROVIRUS AND PROSPECTS FOR VACCINE DEVELOPMENT | 1 Table of Contents 1. Executive summary ....................................................................3 2. Burden of disease and epidemiology 7 a. Burden 7 i. Global burden and trends of diarrheal disease in children and adults 7 ii. The role of norovirus 8 b. Epidemiology 9 i. Early childhood infections 9 ii. Risk factors, modes and settings of transmission 10 iii. Chronic health consequences associated with norovirus infection? 11 c. Challenges in attributing disease to norovirus 12 3. Norovirus biology, diagnostics and their interpretation for field studies and clinical trials..15 a. Norovirus virology 15 i. Genetic diversity, evolution and related challenges for diagnosis 15 ii. -
Virus-Host Interaction: the Multifaceted Roles of Ifitms And
Virus-Host Interaction: The Multifaceted Roles of IFITMs and LY6E in HIV Infection DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Jingyou Yu Graduate Program in Comparative and Veterinary Medicine The Ohio State University 2018 Dissertation Committee: Shan-Lu Liu, MD, PhD, Advisor Patrick L. Green, PhD Jianrong Li, DVM., PhD Jesse J. Kwiek, PhD Copyrighted by Jingyou Yu 2018 Abstract With over 1.8 million newly infected people each year, the worldwide HIV-1 epidemic remains an imperative challenge for public health. Recent work has demonstrated that type I interferons (IFNs) efficiently suppress HIV infection through induction of hundreds of interferon stimulated genes (ISGs). These ISGs target distinct infection stages of invading pathogens and shape innate immunity. Among these, interferon induced transmembrane proteins (IFITMs) and lymphocyte antigen 6 complex, locus E (LY6E) have been shown to differentially modulate viral infections. However, their effects on HIV are not fully understood. In my thesis work, I provided evidence in Chapter 2 showing that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env), thereby inhibiting viral infection. IFITM proteins interacted with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions did not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes led to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appeared to be virus- strain dependent. -
Virus World As an Evolutionary Network of Viruses and Capsidless Selfish Elements
Virus World as an Evolutionary Network of Viruses and Capsidless Selfish Elements Koonin, E. V., & Dolja, V. V. (2014). Virus World as an Evolutionary Network of Viruses and Capsidless Selfish Elements. Microbiology and Molecular Biology Reviews, 78(2), 278-303. doi:10.1128/MMBR.00049-13 10.1128/MMBR.00049-13 American Society for Microbiology Version of Record http://cdss.library.oregonstate.edu/sa-termsofuse Virus World as an Evolutionary Network of Viruses and Capsidless Selfish Elements Eugene V. Koonin,a Valerian V. Doljab National Center for Biotechnology Information, National Library of Medicine, Bethesda, Maryland, USAa; Department of Botany and Plant Pathology and Center for Genome Research and Biocomputing, Oregon State University, Corvallis, Oregon, USAb Downloaded from SUMMARY ..................................................................................................................................................278 INTRODUCTION ............................................................................................................................................278 PREVALENCE OF REPLICATION SYSTEM COMPONENTS COMPARED TO CAPSID PROTEINS AMONG VIRUS HALLMARK GENES.......................279 CLASSIFICATION OF VIRUSES BY REPLICATION-EXPRESSION STRATEGY: TYPICAL VIRUSES AND CAPSIDLESS FORMS ................................279 EVOLUTIONARY RELATIONSHIPS BETWEEN VIRUSES AND CAPSIDLESS VIRUS-LIKE GENETIC ELEMENTS ..............................................280 Capsidless Derivatives of Positive-Strand RNA Viruses....................................................................................................280 -
University of California, Irvine
UNIVERSITY OF CALIFORNIA, IRVINE Deciphering the mechanism of TDP2/VPg unlinkase activity during picornavirus infections DISSERTATION Submitted in partial satisfaction of the requirements for the degree of DOCTOR OF PHILOSOPHY in Biomedical Sciences by Autumn Candace Holmes Dissertation Committee: Dr. Bert L. Semler, Chair Dr. Paul Gershon Dr. Michael McClelland Dr. Suzanne Sandmeyer 2019 © 2019 Autumn C. Holmes TABLE OF CONTENTS Page List of figures iii List of tables v Acknowledgements vi Curriculum vitae vii Abstract of the dissertation ix CHAPTER 1: Introduction Summary 1 Significance 2 Picornavirus translation, RNA synthesis, and role of VPg 9 5’ tyrosyl-DNA phosphodiesterase 2 as VPg unlinkase 20 Biological significance of VPg unlinkase during picornavirus infections 27 CHAPTER 2: Post-translational effects of TDP2 VPg unlinkase activity during picornavirus infection in a human cell model Summary 30 Introduction 31 Results 36 Discussion 71 Materials and Methods 77 CHAPTER 3: Differential patterns of TDP2 and VP1 subcellular localization during picornavirus infections of multiple human cell lines Summary 84 Introduction 85 Results 88 Discussion 106 Materials and Methods 110 CHAPTER 4: Final conclusions and overall significance 112 REFERENCES 120 ii LIST OF FIGURES Page Figure 1.1 Schematic of the picornavirus genome 11 Figure 1.2 Forms of the viral RNA that arise during picornavirus infections and their linkage to VPg 19 Figure 1.3 Cellular roles of TDP2 beyond DNA repair 26 Figure 2.1 Binding of PCBP and 3CDpro to the poliovirus -
Noroviruses Subvert the Core Stress Granule Component G3BP1 to Promote Viral Vpg-Dependent Translation
Washington University School of Medicine Digital Commons@Becker Open Access Publications 8-12-2019 Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation Myra Hosmillo Jia Lu Michael R. McAllaster James B. Eaglesham Xinjie Wang See next page for additional authors Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Authors Myra Hosmillo, Jia Lu, Michael R. McAllaster, James B. Eaglesham, Xinjie Wang, Edward Emmott, Patricia Domingues, Yasmin Chaudhry, Tim J. Fitzmaurice, Matthew K.H. Tung, Marc Dominik Panas, Gerald McInerney, Nicolas Locker, Craig B. Wilen, and Ian G. Goodfellow RESEARCH ARTICLE Noroviruses subvert the core stress granule component G3BP1 to promote viral VPg-dependent translation Myra Hosmillo1†, Jia Lu1†, Michael R McAllaster2†, James B Eaglesham1,3, Xinjie Wang1,4, Edward Emmott1,5,6, Patricia Domingues1, Yasmin Chaudhry1, Tim J Fitzmaurice1, Matthew KH Tung1, Marc Dominik Panas7, Gerald McInerney7, Nicolas Locker8, Craig B Wilen9*, Ian G Goodfellow1* 1Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom; 2Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States; 3Department of Microbiology, Harvard Medical School, Boston, United States; 4Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, China; 5Department of Bioengineering, Northeastern University, Boston, United States; 6Barnett Institute for Chemical -
Investigating the Role of PIR1 and CD200R1 in the Innate Immune Response to Viral Pathogens
University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2017-05-30 Investigating the Role of PIR1 and CD200R1 in the Innate Immune Response to Viral Pathogens Christopher R. MacKay University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Immunity Commons, Immunology of Infectious Disease Commons, Pathogenic Microbiology Commons, and the Virology Commons Repository Citation MacKay CR. (2017). Investigating the Role of PIR1 and CD200R1 in the Innate Immune Response to Viral Pathogens. GSBS Dissertations and Theses. https://doi.org/10.13028/M2602R. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/901 Creative Commons License This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. INVESTIGATING THE ROLE OF PIR1 AND CD200R1 IN THE INNATE IMMUNE RESPONSE TO VIRAL PATHOGENS A Dissertation Presented by CHRISTOPHER ROBERT MACKAY Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY May 30, 2017 M.D./Ph.D. Program INVESTIGATING THE ROLE OF PIR1 AND CD200R1 IN THE INNATE IMMUNE RESPONSE TO VIRAL PATHOGENS A Dissertation Presented by CHRISTOPHER ROBERT MACKAY The signatures of the Dissertation Defense Committee signifies completion and approval as to style and content of the Dissertation Evelyn A. -
Influenza Gastrointestinal Infections
Gastrointestinal Infections Influenza Miranda de Graaf 28 May 2018 [email protected] Viroscience lab, Erasmus MC, Rotterdam, the Netherlands Gastrointestinal infections . Worldwide 3-6 million children die each year from infectious gastroenteritis . Gastrointestinal infections are viral, bacterial or parasitic infections that cause gastroenteritis, an inflammation of the gastrointestinal tract . Symptoms include diarrhea, vomiting, and abdominal pain. Gastrointestinal infections . Which viruses cause gastrointestinal infections . Host defences . Transmission via the fecal-oral route . Tracking transmission . Rotaviruses . Noroviruses . Role of Bacteria . Take home messages Foodborne Illness (USA) Estimated nr FB cases Estimated nr Estimated nr deaths Per 100000 hospitalisations 95% norovirus 95% norovirus 99% norovirus Scallan et al., 2011 Gastrointestinal infections . Norovirus Major outbreaks in children and adults . Rotavirus Major cause of diarrhea in children and infants, Rotavirus is responsible for the most severe cases. Sapovirus Infects children and adults . Astrovirus Infects mainly children <5 years . Adenovirus Infects children much more often. Adenovirus can cause diarrhea. But the most common symptom is respiratory illness Gastrointestinal infections Gastrointestinal infections . Norovirus ssRNA positive strand virus, Non-enveloped . Sapovirus ssRNA positive strand virus, Non-enveloped . Rotavirus dsRNA virus, Non-enveloped . Astrovirus ssRNA positive strand virus, Non-enveloped . Adenovirus dsRNA virus, Non-enveloped -
Synthetic Viruses: a New Opportunity to Understand and Prevent Viral Disease
REVIEW Synthetic viruses: a new opportunity to understand and prevent viral disease Eckard Wimmer1, Steffen Mueller1, Terrence M Tumpey2 & Jeffery K Taubenberger3 Rapid progress in DNA synthesis and sequencing is spearheading the deliberate, large-scale genetic alteration of organisms. These new advances in DNA manipulation have been extended to the level of whole-genome synthesis, as evident from the synthesis of poliovirus, from the resurrection of the extinct 1918 strain of influenza virus and of human endogenous retroviruses and from the restructuring of the phage T7 genome. The largest DNA synthesized so far is the 582,970 base pair genome of Mycoplasma genitalium, although, as yet, this synthetic DNA has not been ‘booted’ to life. As genome synthesis is independent of a natural template, it allows modification of the structure and function of a virus’s genetic information to an extent that was hitherto impossible. The common goal of this new strategy is to further our understanding of an organism’s properties, particularly its pathogenic armory if it causes disease in humans, and to make use of this new information to protect from, or treat, human viral disease. Although only a few applications of virus synthesis have been described as yet, key recent findings have been the resurrection of the 1918 influenza virus and the generation of codon- and codon pair–deoptimized polioviruses. Unprecedented progress in synthesis and sequence analysis of DNA systems (‘refactoring’ genomes) or recoding viral genetic information lies at the heart of the recent transformation of molecular biology for the production of vaccine candidates. and the emergence of the field termed synthetic biology. -
Association with Translation Initiation Factors
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Virology 330 (2004) 487–492 www.elsevier.com/locate/yviro Rapid Communication Proteomics of herpes simplex virus infected cell protein 27: association with translation initiation factors Errin C. Fontaine-Rodrigueza,b, Travis J. Taylora, Melanie Oleskya, David M. Knipea,b,* aDepartment of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA bProgram in Virology, Harvard Medical School, Boston, MA 02115, USA Received 27 July 2004; returned to author for revision 10 September 2004; accepted 4 October 2004 Available online 28 October 2004 Abstract The herpes simplex virus (HSV) immediate early ICP27 protein plays an essential role in stimulating viral early and late gene expression. ICP27 appears to be multifunctional in that it has been reported to stimulate viral late gene transcription, polyadenylation site usage, and RNA export. We report here on proteomic studies involving immunoprecipitation of ICP27 and mass spectrometric identification of co- precipitated proteins. These studies show an association of ICP27 with the cellular translation initiation factors poly A binding protein (PABP), eukaryotic initiation factor 3 (eIF3), and eukaryotic initiation factor 4G (eIF4G) in infected cells. Immunoprecipitation-western blot studies confirmed these associations. Finally, purified MBP-tagged ICP27 (MBP-27) can interact with eIF3 subunits p47 and p116 in vitro. These results suggest that ICP27 may also play a role in stimulating translation of certain viral and host mRNAs and/or in inhibiting host mRNA translation. D 2004 Elsevier Inc. All rights reserved. Keywords: ICP27; eIF4G; eIF3; PABP; Translation initiation Introduction 2002), and shuttles from the nucleus to the cytoplasm (Mears and Rice, 1998; Soliman et al., 1997). -
Glycosphingolipids As Receptors for Non-Enveloped Viruses
Viruses 2010, 2, 1011-1049; doi:10.3390/v2041011 OPEN ACCESS viruses ISSN 1999-4915 www.mdpi.com/journal/viruses Review Glycosphingolipids as Receptors for Non-Enveloped Viruses Stefan Taube †, Mengxi Jiang † and Christiane E. Wobus * Department of Microbiology and Immunology, University of Michigan Medical School, 5622 Medical Sciences Bldg. II, 1150 West Medical Center Dr., Ann Arbor, MI 48109, USA; E-Mails: [email protected] (S.T.); [email protected] (M.J.) † These authors contributed equally to the work. * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-734-647-9599; Fax: +1-734-764-3562. Received: 2 March 2010; in revised form: 09 April 2010 / Accepted: 13 April 2010 / Published: 15 April 2010 Abstract: Glycosphingolipids are ubiquitous molecules composed of a lipid and a carbohydrate moiety. Their main functions are as antigen/toxin receptors, in cell adhesion/recognition processes, or initiation/modulation of signal transduction pathways. Microbes take advantage of the different carbohydrate structures displayed on a specific cell surface for attachment during infection. For some viruses, such as the polyomaviruses, binding to gangliosides determines the internalization pathway into cells. For others, the interaction between microbe and carbohydrate can be a critical determinant for host susceptibility. In this review, we summarize the role of glycosphingolipids as receptors for members of the non-enveloped calici-, rota-, polyoma- and parvovirus families. Keywords: non-enveloped virus; glycosphingolipid; receptor; calicivirus; rotavirus; polyomavirus; parvovirus 1. Introduction Viruses come in many different flavors and are often broadly classified based on their nucleic acid content (DNA versus RNA virus), capsid symmetry (icosahedral, helical, or complex), and the presence or absence of a lipid envelope (enveloped versus non-enveloped). -
Animal Enteric Viruses: Gene Expression, Epidemiology and Their
ANIMAL ENTERIC VIRUSES: GENE EXPRESSION, EPIDEMIOLOGY AND THEIR ROLE IN SHELLFISH AND ENVIRONMENTAL CONTAMINATION DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Verónica P. Costantini, BS ******* The Ohio State University 2007 Dissertation Committee: Distinguished University Professor Dr. Linda J Saif, Adviser Professor Dr. Daral J. Jackwood Associate Professor Dr John H Hughes Approved by Adviser Graduate Program in Veterinary Preventive Medicine Copyright by Verónica Costantini 2007 ABSTRACT Acute gastroenteritis (AGE) is one of the most common diseases worldwide. Seven to 41 percent of these are food-borne disease. Each year, foodborne diseases cause 76 million illnesses, more than 300,000 hospitalizations and 5,000 deaths in the U.S, indicating that 1 in 4 Americans develop disease and at least 1 in 1000 is hospitalized. Only 20-30% of these illnesses are attributed to known pathogens, and viral agents are estimated to account for more than 2/3 of these. Among viruses, noroviruses (NoVs) are estimated to cause 82% of the foodborne illnesses. HuNoVs have been detected in fruits, vegetables, ready-to-eat foods and seafood worldwide. Ten to 70% of outbreaks are associated with seafood and contamination occurs at pre- and post-harvest. However, no data has been collected to determine viral contamination in commercial shellfish harvesting areas throughout the U.S. coasts. In addition, although the identification of related animal enteric caliciviruses and recombinants have raised concerns for human infection or co-infection with different strains, the presence of animal strains in shellfish with potential risk for humans has not been studied.