DOCSLIB.ORG

Single-Cell Analysis of Influenza a Virus Replication

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Single-Cell Analysis of Influenza a Virus Replication Single-Cell Analysis of Influenza A Virus Replication: Sources of Cell-to-Cell Heterogeneity and Discovery of a Novel Type of Defective Interfering Particle Dissertation zur Erlangung des akademischen Grades Doktoringenieur (Dr.-Ing.) von: Dipl.-Ing. Sascha Young Kupke geboren am: 31. Oktober 1984 in Berlin genehmigt durch die Fakultät für Verfahrens- und Systemtechnik der Otto-von-Guericke Universität Magdeburg Promotionskommission: Prof. Dr.-Ing. Kai Sundmacher (Vorsitz) Prof. Dr.-Ing. Udo Reichl (Gutachter) Prof. John Yin (Gutachter) Dr. Hansjörg Hauser (Gutachter) eingereicht am: 08. März 2019 Promotionskolloquium am: 05. Februar 2020 II Abstract Abstract Influenza A viruses (IAVs) cause respiratory disease and are a major human pathogen that can give rise to a high morbidity. Besides annual epidemics, IAVs can occasionally also cause a more severe pandemic. Typically, the best protection against the flu is provided by annual vaccination. One way to produce human influenza vaccines are cell culture-based manufacturing systems. Naturally, the smallest production unit in such a process is the infected single cell. However, it is well known that cells in a seemingly homogenous population display a vast cell-to-cell heterogeneity. In the context of this PhD work, we conducted single-cell analysis of IAV-infected cells for applications in cell culture-based influenza virus production. Specifically, we studied the cell-to-cell variability in virus titers to gain a deeper understanding and an improved description of the process. Moreover, we strived for a comprehension of high- productive single cells to possibly derive strategies to improve the production yield. Therefore, we devised a single-cell analysis workflow for IAV-infected cells. For this, we isolated single IAV-infected Madin-Darby canine kidney (MDCK) cells in 384 well plates using a limiting dilution approach, in which single cells in individual wells were identified by microscopy. After incubation, virus titers in the supernatant were investigated by plaque assay and intracellular parameters by real-time reverse transcription quantitative PCR and conventional RT-PCR. The procedure enabled (i) absolute quantification of virus titers and intracellular genomic viral RNAs (vRNAs), (ii) a good throughput of single-cell measurements, (iii) no apparent perturbation of cellular behavior despite the processing and isolation of single cells, and (iv) multiparametric correlation of the single-cell virus yield to either: the cell size, ribosomal RNAs, up to four different genomic vRNAs (simultaneously), or to intracellular defective interfering (DI) RNAs on up to three viral genome segments (simultaneously). In future studies, we may couple our experimental platform to single-cell RNA sequencing (via next-generation sequencing technologies) to study the whole-cell transcriptome of IAV-infected cells, and specifically, to compare the transcriptomic information to the single-cell virus titer. Next, the established single-cell analysis procedure was used to study cell-to-cell variability in IAV replication. We observed a vast heterogeneity with virus titers that ranged from 1 to about 1000 plaque-forming units per cell, and intracellular vRNAs that showed quantitative differences which spanned almost three orders of magnitude. We further showed that cell-to- cell heterogeneity in IAV replication can be generated by both, the inherent randomness in biochemical reactions (i.e., sources of intrinsic noise) and deterministic factors (i.e., sources of extrinsic noise). The latter are (yet unknown) properties, different between individual cells, that III Abstract can affect virus replication in each cell differently. However, more research in single-cell virology is required to resolve the contribution of stochasticity to the cell-to-cell heterogeneity in virus replication (in comparison to the contribution caused by sources of extrinsic noise). Taken together, we show that virus infections are highly variable at the single cell level, and that cell population-based experiments are not covering crucial aspects of virus infections. Next, we investigated potential deterministic sources of the large cell-to-cell heterogeneity in virus titers. We showed that differences in the cell size and the ribosome content did not appear to affect the virus yield of a single cell. Moreover, the between-cell variability in the properties of individual cells (present in the non-clonal MDCK cell line) did also not seem to account for the large single-cell diversity in IAV replication. Finally, we showed that the virus- to-virus genetic heterogeneity (of the infecting virus population) did also not appear to influence the cell-to-cell heterogeneity in IAV replication, except for defective interfering particles (DIPs). DIPs are defective, non-infectious virus particles that harbor a deleted form of the viral RNA genome, which interfere with the replication of their homologous standard virus. More specifically, we demonstrated that the content of such deleted DI RNAs in an infected single cell can influence the cell-specific virus titer. However, our results also indicated that additional unknown factors may further affect the cell-to-cell variability in IAV replication, which remain to be elucidated. Altogether, our results advance single-cell virology research towards an understanding of the large cell-to-cell heterogeneity in virus infections. Finally, utilizing single-cell analysis, we discovered (and enriched) a novel type of IAV-derived DIP, termed “OP7” virus. Conventional DIPs (cDIPs) typically harbor a large internal deletion in one genomic vRNA, whereas OP7 virus contained various point mutations in segment 7 (S7) vRNA. These substitutions affected the promotor regions, encoded proteins, and genome packaging signals. We further characterized OP7 virus replication at different intracellular viral life cycle steps in cell-population-based experiments. Most importantly, similar to cDIPs, OP7 virus showed strong interference with replication of various IAV strains, including relevant epidemic and pandemic human IAV strains. Moreover, we demonstrated that OP7 virus can also interfere with IAV replication in human cell lines. Therefore, we believe that OP7 virus may be a promising candidate for antiviral therapy. Future research efforts may focus on gathering mechanistic insights into OP7 virus molecular biology, animal trials (e.g. in mice and in ferrets) to investigate its antiviral potential, and the development of cell culture-based manufacturing of OP7 virus. IV Kurzfassung Kurzfassung Influenza A Viren (IAV) verursachen Atemwegserkrankungen und sind ein bedeutendes humanes Pathogen, welches zu einem hohen Erkrankungsrate führen kann. Neben der jährlichen Epidemie können IAV auch gelegentlich zu schweren Pandemien führen. Üblicherweise wird der beste Schutz gegen die Grippe durch eine jährliche Impfung gewährleistet. Eine Möglichkeit, humane Influenza Impfstoffe zu produzieren, sind zellkulturbasierte Herstellungssysteme. Selbstverständlich ist die kleinste Produktionseinheit in solch einem Prozess die infizierte Einzelzelle. Es ist jedoch bekannt, dass Zellen in einer scheinbar homogenen Population eine enorme Heterogenität von Zelle zu Zelle aufweisen. Im Kontext dieser Doktorarbeit haben wir die Einzelzellanalyse von IAV-infizierten Zellen für mögliche Anwendungen in der zellkulturbasierten Influenzavirus Produktion durchgeführt. Insbesondere haben wir die Variabilität in den Virustitern zwischen den Zellen untersucht, um ein besseres Verständnis und eine verbesserte Beschreibung des Prozesses zu erreichen. Weiterhin haben wir ein Verständnis von hochproduktiven Einzelzellen angestrebt, um gegebenenfalls Strategien für eine höhere Produktionsausbeute abzuleiten zu können. Aus diesem Grund haben wir einen Workflow zur Einzelzellanalyse für IAV-infizierte Zellen entwickelt. Hierfür haben wir einzelne, IAV-infizierte Madin-Darby canine kidney (MDCK) Zellen in 384 Well Platten mit Hilfe eines „limitierenden Verdünnungsansatzes“ isoliert, in welchem wir die Einzelzellen (in einzelnen Wells) mikroskopisch identifiziert haben. Nach der Inkubation wurden die Virustiter in den Überständen mit Hilfe des Plaque Tests quantifiziert und intrazelluläre Parameter durch quantitative real-time reverse Transkription PCR und der konventionellen RT-PCR untersucht. Die Prozedur ermöglicht (i) die absolute Quantifizierung von Virustitern und intrazellulärer genomischer viraler RNA (vRNA), (ii) einen guten Durchsatz an Einzelzellmessungen, (iii) keine offensichtliche Störung des zellulären Verhaltens trotz der Verarbeitung und Isolierung von Einzelzellen und (iv) eine multiparametrische Korrelation des Virustiters mit: der Größe der Zelle, ribosomalen RNAs, bis zu vier verschiedenen genomischen vRNAs (gleichzeitig) oder mit intrazellulären defekt-interferierenden (DI) RNAs von drei verschiedenen Genomsegmenten (gleichzeitig). In zukünftigen Studien könnten wir unsere experimentelle Plattform mit der Einzelzell-RNA Sequenzierung (mit Hilfe von „next-generation“ Sequenziertechnologien) koppeln, um das Gesamtzelltranskriptom von IAV-infizierten Einzelzellen zu untersuchen und insbesondere, um die transkriptomische Informationen mit dem Einzelzelltiter zu vergleichen. V Kurzfassung Anschließend wurde die etablierte Prozedur für die Einzelzellanalyse verwendet, um die Variabilität in der IAV Replikation von Zelle zu Zelle zu untersuchen. Wir haben eine enorme Heterogenität beobachtet. Die Virustiter reichten von 1
Load more

Recommended publications
  • 1 Chapter I Overall Issues of Virus and Host Evolution
    CHAPTER I OVERALL ISSUES OF VIRUS AND HOST EVOLUTION tree of life. Yet viruses do have the This book seeks to present the evolution of characteristics of life, can be killed, can become viruses from the perspective of the evolution extinct and adhere to the rules of evolutionary of their host. Since viruses essentially infect biology and Darwinian selection. In addition, all life forms, the book will broadly cover all viruses have enormous impact on the evolution life. Such an organization of the virus of their host. Viruses are ancient life forms, their literature will thus differ considerably from numbers are vast and their role in the fabric of the usual pattern of presenting viruses life is fundamental and unending. They according to either the virus type or the type represent the leading edge of evolution of all of host disease they are associated with. In living entities and they must no longer be left out so doing, it presents the broad patterns of the of the tree of life. evolution of life and evaluates the role of viruses in host evolution as well as the role Definitions. The concept of a virus has old of host in virus evolution. This book also origins, yet our modern understanding or seeks to broadly consider and present the definition of a virus is relatively recent and role of persistent viruses in evolution. directly associated with our unraveling the nature Although we have come to realize that viral of genes and nucleic acids in biological systems. persistence is indeed a common relationship As it will be important to avoid the perpetuation between virus and host, it is usually of some of the vague and sometimes inaccurate considered as a variation of a host infection views of viruses, below we present some pattern and not the basis from which to definitions that apply to modern virology.
    [Show full text]
  • HIV-1) CD4 Receptor and Its Central Role in Promotion of HIV-1 Infection
    MICROBIOLOGICAL REVIEWS, Mar. 1995, p. 63–93 Vol. 59, No. 1 0146-0749/95/$04.0010 Copyright q 1995, American Society for Microbiology The Human Immunodeficiency Virus Type 1 (HIV-1) CD4 Receptor and Its Central Role in Promotion of HIV-1 Infection STEPHANE BOUR,* ROMAS GELEZIUNAS,† AND MARK A. WAINBERG* McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, and Departments of Microbiology and Medicine, McGill University, Montreal, Quebec, Canada H3T 1E2 INTRODUCTION .........................................................................................................................................................63 RETROVIRAL RECEPTORS .....................................................................................................................................64 Receptors for Animal Retroviruses ........................................................................................................................64 CD4 Is the Major Receptor for HIV-1 Infection..................................................................................................65 ROLE OF THE CD4 CORECEPTOR IN T-CELL ACTIVATION........................................................................65 Structural Features of the CD4 Coreceptor..........................................................................................................65 Interactions of CD4 with Class II MHC Determinants ......................................................................................66 CD4–T-Cell Receptor Interactions during T-Cell Activation
    [Show full text]
  • Defective Interfering Particles and Their Role in Disease Progression and Persistence
    Volume 1, Issue 2 Review Article ISSN: 2572-9365 Defective Interfering Particles and Their Role in Disease Progression and Persistence Alemayehu Reta Department of Medical Laboratory Science, College of Health Sciences, Debre Markos University, PO Box 269, Debre Markos, Ethiopia *Corresponding Author: Alemayehu Reta, Department of Medical Laboratory Science, College of Health Sciences, Debre Markos University, PO Box 269, Debre Markos, Ethiopia, Email: [email protected] Received: 10 June 2017; Accepted: 23 June 2017; Published: 27 June 2017 Abstract Defective interfering particles (DIPs) are products of inner deletion mutants of viruses that reproduce at the disbursement of the parent virus. This review article aimed at reviewing current science on DIPs of their molecular and immunological features, role in disease progression and persistence, impact on vaccine production and viral vectors, and future directions. Defective interfering particles are very important to the field of biotechnology and genetic engineering due to their nature of stimulating the immune system and attenuating some of the live viruses during live-attenuated vaccine production, however, they have a devastating effect like interfering with vaccine production, that is decreasing the viral titer, and facilitate pathogenesis and persistence of some viral infections. Keywords: Defective Interfering Particles; Persistence; Virus 1. Introduction Viruses are DNA or RNA fragments covered by protein that are incapable to reproduce independently rather they replicate within cells by using the genetic machinery of those cells. During 1947 Von Magnus discovered incomplete particles after he performs consecutive unmixed passages of influenza viruses [1]. Nayak supports Von Magnus experiment by preparing chicken embryo cells and making it to be infected with equine influenza virus, in the first 10hr he obtained the whole RNA component of infectious virus, but after 20 to 30 hours the virus released was Von Magnus type and contained the RNAs of incomplete virus.
    [Show full text]
  • Viral Interference with Antigen Presentation Jonathan W
    REVIEW Viral interference with antigen presentation Jonathan W. Yewdell1 and Ann B. Hill2 CD8+ T cells play an important role in immunity T cells (which were later shown to be CD8+) were demonstrated to be to viruses. Just how important these cells are is responsible for the recovery of mice from acute mousepox (ectromelia) 1–3 + demonstrated by the evolution of viral strategies infection . Subsequently, we have learned that CD8 T cells are impor- tant in mouse immunity to many viruses. CD8+ T cells exert antiviral for blocking the generation or display of pep- effects via the localized secretion of molecules in close vicinity to the tide–major histocompatibility complex class I virus-infected APC (professional or not). Many CD8+ T cells kill APCs complexes on the surfaces of virus-infected cells. by releasing perforin and granzymes (if APCs express Fas, engagement by Fas ligand on CD8+ T cells can also induce lysis). In addition, near- Here, we focus on viral interference with antigen ly all CD8+ T cells secrete IFN-γ and tumor necrosis factor-α (TNF-α) presentation; in particular we consider the impor- (a small percentage of cells secrete IFN-γ only), which induces a potent tance (and difficulty) of establishing the evolu- antiviral state in cells. tionary significance (that is, the ability to enhance It is important to emphasize that CD8+ T cells are but one of many http://www.nature.com/natureimmunology weapons deployed by the immune system to combat viruses. NK cells, viral transmission) of viral gene products that CD4+ T cells and antibody all participate in antiviral immunity.
    [Show full text]
  • (RIG-I) and TLR7 and Metapneumovi
    Cell Type-Specific Recognition of Human Metapneumoviruses (HMPVs) by Retinoic Acid-Inducible Gene I (RIG-I) and TLR7 and Viral Interference of RIG-I Ligand This information is current as Recognition by HMPV-B1 Phosphoprotein of October 2, 2021. Nadege Goutagny, Zhaozhao Jiang, Jane Tian, Peggy Parroche, Jeanne Schickli, Brian G. Monks, Nancy Ulbrandt, Hong Ji, Peter A. Kiener, Anthony J. Coyle and Katherine A. Fitzgerald Downloaded from J Immunol 2010; 184:1168-1179; Prepublished online 30 December 2009; doi: 10.4049/jimmunol.0902750 http://www.jimmunol.org/content/184/3/1168 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2009/12/30/jimmunol.090275 Material 0.DC1 References This article cites 55 articles, 27 of which you can access for free at: http://www.jimmunol.org/content/184/3/1168.full#ref-list-1 by guest on October 2, 2021 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2010 by The American Association of Immunologists, Inc. All rights reserved.
    [Show full text]
  • Innate Immune Response and Viral Interference Strategies Developed by Human Herpesviruses
    Biochemical Pharmacology 80 (2010) 1955–1972 Contents lists available at ScienceDirect Biochemical Pharmacology journal homepage: www.elsevier.com/locate/biochempharm Review Innate immune response and viral interference strategies developed by Human Herpesviruses Patricia Vandevenne, Catherine Sadzot-Delvaux, Jacques Piette * Laboratory of Virology and Immunology, GIGA-Research B34, University of Lie`ge, B-4000 Lie`ge, Belgium ARTICLE INFO ABSTRACT Article history: Viruses are by far the most abundant parasites on earth and they have been found to infect animals, Received 28 April 2010 plants and bacteria. However, different types of viruses can only infect a limited range of hosts and many Accepted 1 July 2010 are species-specific. Herpesviruses constitute a large family of DNA viruses that cause diseases in animals, including humans and that are known to undergo lytic or latent infections. Consequently, they Keywords: developed numerous strategies to counteract host antiviral responses to escape immune surveillance. Herpesviruses Innate immune response constitutes the first line of host defence that limits the viral spread and also Innate immune response plays an important role in the activation of adaptive immune response. Viral components are recognized Viral evasion by specific host Pathogen Recognition Receptors (PRRs) which trigger the activation of IRF3, NF-kB and IFN-a/-b IRF3 AP-1, three regulators of IFN-b expression. IFN-b is responsible for the induction of Interferon- NF-kB Stimulated Genes (ISGs) that encode antiviral effectors important to limit the viral spread and to establish an antiviral state as well in the infected cells as in the neighbouring non-infected cells. In this review, we will summarize how host cells recognize viral components and activate downstream signalling pathways leading to the production of IFN-b and ISGs.
    [Show full text]
  • State of the Art of New Vaccine Research and Development
    WHO/IVB/06.01 ORIGINAL: ENGLISH State of the art of new vaccine Iresearch and development VImmunization,B Vaccines and Biologicals WHO/IVB/06.01 ORIGINAL: ENGLISH State of the art of new vaccine Iresearch and development VImmunization,B Vaccines and Biologicals The Department of Immunization, Vaccines and Biologicals thanks the donors whose unspecified financial support has made the production of this document possible. This document was produced by the Initiative for Vaccine Research of the Department of Immunization, Vaccines and Biologicals Ordering code: WHO/IVB/06.01 Printed: January 2006 This publication is available on the Internet at: www.who.int/vaccines-documents/ Copies may be requested from: World Health Organization Department of Immunization, Vaccines and Biologicals CH-1211 Geneva 27, Switzerland • Fax: + 41 22 791 4227 • Email: [email protected] • © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel: +41 22 791 3264; fax: +41 22 791 4857; email: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; email: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.
    [Show full text]
  • Genome Replication Dynamics of a Bacteriophage and Its Satellite Reveal Strategies for Parasitism and Viral Restriction
    bioRxiv preprint doi: https://doi.org/10.1101/639039; this version posted May 17, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Genome replication dynamics of a bacteriophage and its satellite reveal strategies for parasitism and viral restriction Zachary K Barth1, Tania V Silvas1, Angus Angermeyer1, Kimberley D Seed1,2,* 1Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA 2 Chan Zuckerberg Biohub, San Francisco, CA 94158, USA * To whom correspondence should be addressed Tel: +1510664e7711, Email: [email protected] ABSTRACT Phage-inducible chromosomal island-like elements (PLEs) are bacteriophage satellites found in Vibrio cholerae. PLEs parasitize the lytic phage ICP1, excising from the bacterial chromosome, replicating, and mobilizing to new host cells following cell lysis. PLEs protect their host cell populations by completely restricting the production of ICP1 progeny. Previously, it was found that ICP1 replication was reduced during PLE(+) infection. Despite robustly replicating its genome, PLE produces relatively few transducing units, leading us to investigate if PLE DNA replication itself is antagonistic to ICP1 replication. Here we identify key constituents of PLE replication and assess their role in interference of ICP1. PLE encodes a RepA_N initiation factor that is sufficient to drive replication from the PLE origin of replication during ICP1 infection. In contrast to previously characterized bacteriophage satellites, expression of the PLE initiation factor was not sufficient for PLE replication in the absence of phage.
    [Show full text]
  • Natural Variation in Resistance to Virus Infection in Dipteran Insects
    viruses Review Natural Variation in Resistance to Virus Infection in Dipteran Insects William H. Palmer 1,†, Finny S. Varghese 2,3,† and Ronald P. van Rij 2,3,* ID 1 Institute of Evolutionary Biology and Centre for Infection, Evolution and Immunity, University of Edinburgh, Edinburgh EH9 3FL UK; [email protected] 2 Department of Medical Microbiology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands; [email protected] 3 Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen 6525 GA, The Netherlands * Correspondence: [email protected] † These authors contributed equally to this manuscript. Received: 10 February 2018; Accepted: 8 March 2018; Published: 9 March 2018 Abstract: The power and ease of Drosophila genetics and the medical relevance of mosquito- transmitted viruses have made dipterans important model organisms in antiviral immunology. Studies of virus–host interactions at the molecular and population levels have illuminated determinants of resistance to virus infection. Here, we review the sources and nature of variation in antiviral immunity and virus susceptibility in model dipteran insects, specifically the fruit fly Drosophila melanogaster and vector mosquitoes of the genera Aedes and Culex. We first discuss antiviral immune mechanisms and describe the virus-specificity of these responses. In the following sections, we review genetic and microbiota-dependent variation in antiviral immunity. In the final sections, we explore less well-studied sources of variation, including abiotic factors, sexual dimorphism, infection history, and endogenous viral elements. We borrow from work on other pathogen types and non-dipteran species when it parallels or complements studies in dipterans.
    [Show full text]
  • Viral Interference: a Review
    The Pharma Innovation Journal 2020; 9(10): 421-428 ISSN (E): 2277- 7695 ISSN (P): 2349-8242 NAAS Rating: 5.03 Viral interference: A review TPI 2020; 9(10): 421-428 © 2020 TPI www.thepharmajournal.com Ojasvita, Himanshu Sharma, Anupama Deora, Vandna Bhanot, Anshul Received: 15-06-2020 Accepted: 21-08-2020 Lather, Rajendra Yadav, Pankaj Kumar, Dinesh Mittal, Vijay and Satbir Sharma Ojasvita Department of Department of Veterinary Microbiology, Abstract LUVAS, Hisar, Haryana, India The inhibition of viral reproduction caused by previous exposure of cells to another virus is popularly known as viral interference or superinfection resistance. The primary virus infecting the cell prevents the Himanshu Sharma replication of secondary virus in that cell, thus making viral interference a very important phenomenon in Department of Animal viral world. It may be simplified by stating that the virus can suppress the shedding of a new virus of the Husbandry, Uttar Pradesh, homologous or heterologous type which enters the cell. The mechanisms proposed to explain viral India interference may be briefly described as competing by attachment interference where receptors for the superinfecting virus are reduced or blocked, competing for intracellular components required for Anupama Deora replication of the host machinery and virus induced interferon interference. The intensity of viral Department of FTL, NIFTEM, Sonipat, Haryana, India interference however depends on several factors such as adaptation of viruses to host species, pathogenicity of viruses, time of co-infection, and environmental factors. This review highlights the Vandna Bhanot importance of testing of interfering viruses during the molecular screening and viral isolation attempts of Disease Investigation infected poultry flocks and other animals so as to identify the consequences of interference during Laboratory, LUVAS, Ambala, coinfection.
    [Show full text]
  • Proquest Dissertations
    Host structuring of parasite populations: Some theoretical and computational studies Item Type text; Dissertation-Reproduction (electronic) Authors Taylor, Jesse Earl Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 03/10/2021 11:51:04 Link to Item http://hdl.handle.net/10150/289991 HOST STRUCTURING OF PARASITE POPULATIONS: SOME THEORETICAL AND COMPUTATIONAL STUDIES by Jesse Earl Taylor A Dissertation Submitted to the Faculty of the DEPARTMENT OF ECOLOGY AND EVOLUTIONARY BIOLOGY In Partial Fulfillment of the Requirements For the Degree of DOCTOR OF PHILOSOPHY In the Graduate College THE UNIVERSITY OF ARIZONA 2 0 0 3 UMI Number: 3108960 INFORMATION TO USERS The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. UMI UMI Microform 3108960 Copyright 2004 by ProQuest Information and Learning Company. All rights reserved.
    [Show full text]
  • Viral Interactions with Adaptor-Protein Complexes: a Ubiquitous Trait Among Viral Species
    International Journal of Molecular Sciences Review Viral Interactions with Adaptor-Protein Complexes: A Ubiquitous Trait among Viral Species Ivana Strazic Geljic 1,2 , Paola Kucan Brlic 1,3 , Lucija Musak 2 , Dubravka Karner 1, Andreja Ambriovi´c-Ristov 4 , Stipan Jonjic 1,3, Peter Schu 5 and Tihana Lenac Rovis 1,* 1 Center for Proteomics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia; [email protected] (P.K.B.); [email protected] (D.K.); [email protected] (S.J.) 2 Fidelta Ltd., Prilaz baruna Filipovica 29, 10000 Zagreb, Croatia; Ivana.StrazicGeljic@fidelta.eu (I.S.G.); Lucija.Musak@fidelta.eu (L.M.) 3 Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia 4 Laboratory for Cell Biology and Signalling, Division of Molecular Biology, Ruder¯ Boškovi´cInstitute, Bijeniˇcka54, 10000 Zagreb, Croatia; [email protected] 5 Department of Cellular Biochemistry, University Medical Center, Georg-August-University Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany; [email protected] * Correspondence: [email protected]; Tel.: +385-51-651-260 Abstract: Numerous viruses hijack cellular protein trafficking pathways to mediate cell entry or to rearrange membrane structures thereby promoting viral replication and antagonizing the im- mune response. Adaptor protein complexes (AP), which mediate protein sorting in endocytic and secretory transport pathways, are one of the conserved viral targets with many viruses possessing AP-interacting motifs. We present here different mechanisms of viral interference with AP complexes and the functional consequences that allow for efficient viral propagation and evasion of host immune Citation: Strazic Geljic, I.; Kucan Brlic, P.; Musak, L.; Karner, D.; defense.
    [Show full text]