DOCSLIB.ORG

Characterization of Molecular Targets for Differential Regulation of the Type I and III Interferon Induction and Signalling Pathways by Rotavirus NSP1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Characterization of Molecular Targets for Differential Regulation of the Type I and III Interferon Induction and Signalling Pathways by Rotavirus NSP1 Characterization of molecular targets for differential regulation of the type I and III interferon induction and signalling pathways by rotavirus NSP1 Thesis submitted in accordance with the requirements of the University of Liverpool for the degree of Doctor in Philosophy by Gennaro Iaconis September 2018 Table of contents TABLE OF CONTENTS ............................................................................................................................... 1 LIST OF FIGURES ...................................................................................................................................... 6 LIST OF TABLES ........................................................................................................................................ 8 DECLARATION ....................................................................................................................................... 10 ABSTRACT ............................................................................................................................................. 11 1 INTRODUCTION ........................................................................................................................... 12 1.1 Rotavirus ................................................................................................................. 12 1.1.1 Historical Background ......................................................................................... 12 1.1.2 Classification ....................................................................................................... 13 1.1.2.1 Reoviridae ...................................................................................................... 13 1.1.2.1.1 Rotavirus ................................................................................................ 14 1.1.3 Epidemiology ...................................................................................................... 16 1.1.4 Pathogenesis and pathology ............................................................................... 18 1.1.5 Rotavirus vaccine ................................................................................................ 19 1.1.6 Virion Structure ................................................................................................... 20 1.1.7 Genome organization ......................................................................................... 24 1.1.8 Gene-protein coding assignments ...................................................................... 25 1.1.9 Rotavirus proteins ............................................................................................... 26 1.1.9.1 Rotavirus structural proteins (VPs) ................................................................ 26 1.1.9.1.1 VP1 (core) ............................................................................................... 26 1.1.9.1.2 VP2 (core) ............................................................................................... 26 1.1.9.1.3 VP3 (core) ............................................................................................... 27 1.1.9.1.4 VP4 (outer capsid protein) ..................................................................... 27 1.1.9.1.5 VP6 (inner capsid protein) ..................................................................... 28 1.1.9.1.6 VP7 (outer capsid protein) ..................................................................... 28 1.1.9.2 Rotavirus non-structural proteins (NSPs) ...................................................... 29 1.1.9.2.1 NSP1 ....................................................................................................... 29 1.1.9.2.2 NSP2 ....................................................................................................... 31 1.1.9.2.3 NSP3 ....................................................................................................... 33 1.1.9.2.4 NSP4 ....................................................................................................... 33 1.1.9.2.5 NSP5 ....................................................................................................... 35 1.1.9.2.6 NSP6 ....................................................................................................... 35 1.1.10 Rotavirus replication cycle .................................................................................. 37 1.1.10.1 Virus attachment ......................................................................................... 39 1.1.10.2 Penetration .................................................................................................. 40 1.1.10.3 Uncoating ..................................................................................................... 41 1 1.1.10.4 Transcription ................................................................................................ 41 1.1.10.5 Translation ................................................................................................... 42 1.1.10.6 Viroplasms formation and genome replication ........................................... 43 1.1.10.7 Virion assembly, maturation and release .................................................... 44 1.2 Interferon ................................................................................................................ 47 1.2.1 Toll-like receptors ............................................................................................... 52 1.2.2 RIG-I receptors .................................................................................................... 56 1.2.2.1 RIG-I ............................................................................................................... 57 1.2.2.2 MDA5 ............................................................................................................. 57 1.2.2.3 LGP2 ............................................................................................................... 57 1.2.3 MAVS .................................................................................................................. 58 1.2.4 Regulation of the IFN: promoters and induction ................................................ 59 1.2.5 Structure of the promoter of Type I IFN ............................................................. 59 1.2.6 Structure of the promoter of Type III IFN ........................................................... 59 1.2.7 JAK / STAT pathway ............................................................................................ 64 1.3 Modulation of the host innate immunity by rotavirus NSP1 .................................... 65 1.3.1 IRFs ...................................................................................................................... 66 1.3.2 RIG-I, MDA5 and MAVS ....................................................................................... 67 1.3.3 NF-κB ................................................................................................................... 67 1.3.4 STAT1 and STAT2 ................................................................................................ 68 1.4 Aims ........................................................................................................................ 70 2 MATERIAL AND METHODS ........................................................................................................... 72 2.1 Cell Culture .............................................................................................................. 72 2.1.1 Cell lines .............................................................................................................. 72 2.1.2 Maintenance of cells in tissue culture ................................................................ 73 2.1.3 Maintenance of stable cells in tissue culture...................................................... 73 2.1.4 Transfection ........................................................................................................ 73 2.2 Viruses .................................................................................................................... 74 2.2.1 Sendai virus ......................................................................................................... 74 2.2.2 Classical Swine fever Virus .................................................................................. 74 2.2.3 CSFV infection of PK-15 cell lines ........................................................................ 74 2.2.4 Modified Vaccinia Ankara –T7 polymerase (MVA-T7) ........................................ 74 2.3 Cloning and plasmid preparation ............................................................................ 75 2 2.3.1 Polymerase chain reaction (PCR) ........................................................................ 75 2.3.2 Agarose gel electrophoresis ................................................................................ 76 2.3.3 Gel purification of DNA ....................................................................................... 76 2.3.4 Restriction enzyme digestion of DNA ................................................................. 76 2.3.5 Dephosphorylation of vector DNA ...................................................................... 77 2.3.6 DNA ligation ........................................................................................................ 77 2.3.7 Transformation ..................................................................................................
Load more

Recommended publications
  • Formation of Virus-Like Particles from Human Cell Lines Exclusively Expressing Influenza Neuraminidase
    Journal of General Virology (2010), 91, 2322–2330 DOI 10.1099/vir.0.019935-0 Formation of virus-like particles from human cell lines exclusively expressing influenza neuraminidase Jimmy C. C. Lai,1 Wallace W. L. Chan,1 Franc¸ois Kien,1 John M. Nicholls,2 J. S. Malik Peiris1,3 and Jean-Michel Garcia1 Correspondence 1HKU-Pasteur Research Centre, Hong Kong SAR Jean-Michel Garcia 2Department of Pathology, The University of Hong Kong, Hong Kong SAR [email protected] 3Department of Microbiology, The University of Hong Kong, Hong Kong SAR The minimal virus requirements for the generation of influenza virus-like particle (VLP) assembly and budding were reassessed. Using neuraminidase (NA) from the H5N1 and H1N1 subtypes, it was found that the expression of NA alone was sufficient to generate and release VLPs. Biochemical and functional characterization of the NA-containing VLPs demonstrated that they were morphologically similar to influenza virions. The NA oligomerization was comparable to that of the live virus, and the enzymic activity, whilst not required for the release of NA-VLPs, was Received 8 January 2010 preserved. Together, these findings indicate that NA plays a key role in virus budding and Accepted 23 May 2010 morphogenesis, and demonstrate that NA-VLPs represent a useful tool in influenza research. INTRODUCTION membrane. HA binds to sialic acid receptors on the cell surface and mediates the fusion process (Matrosovich et al., Influenza A viruses are lipid-enveloped members of the 2006), whereas NA cleaves the terminal sialic acids from family Orthomyxoviridae. They contain eight negative-sense, the cell-surface glycans to facilitate release of the progeny single-stranded RNA segments encoding ten viral proteins.
    [Show full text]
  • Reverse Genetic Strategies to Interrogate Reassortment Restriction Among Group a Rotaviruses
    REVERSE GENETIC STRATEGIES TO INTERROGATE REASSORTMENT RESTRICTION AMONG GROUP A ROTAVIRUSES BY JESSICA R. HALL A Thesis Submitted to the Graduate FACulty of WAKE FOREST UNIVERSITY GRADUATE SCHOOL OF ARTS AND SCIENCES in PArtiAl Fulfillment of the Requirements for the Degree of MASTER OF SCIENCE Biology August 2019 Winston-SAlem, North Carolina Approved By: SArah M. MCDonald, Ph.D., Advisor GloriA K. Muday, Ph.D., Chair DouglAs S. Lyles, Ph.D. JAmes B. PeAse, Ph.D. ACKNOWLEDGEMENTS This body of work wAs mAde possible by the influences of Countless people including, but not limited to, those named here. First, I Am thankful for my Advisor, Dr. SArah MCDonald, who paved wAy for this opportunity. Her infeCtious enthusiAsm for sCience served As A Consistent reminder to “keep getting baCk on the horse”. I Am grateful for my Committee members, Drs. DouglAs Lyles, GloriA Muday, And JAmes PeAse whose input And AdviCe Aided in my development into A CAreful sCientist who thinks CritiCAlly About her work. I Am Also thankful for Continued mentorship from my undergraduate reseArch advisor, Dr. NAthan Coussens, whose enthusiAsm for sCience inspired mine. I Am AppreCiAtive of All of my friends for their unyielding support. I Am blessed to have A solid foundation in my FAmily, both blood And Chosen. I Am thankful for my mother, LiAna HAll, who instilled in me my work ethiC And whose pride in me has inspired me to keep pursuing my dreAms. I Am forever indebted to Dr. DiAna Arnett, who has served As my personal And sCientifiC role model; thank you for believing in me, investing in me, And shaping me into the person and sCientist I am today.
    [Show full text]
  • Development of a Real-Time Reverse Transcription
    DEVELOPMENT AND EVALUATION OF A REAL-TIME POLYMERASE CHAIN REACTION ASSAY FOR EQUINE ENCEPHALOSIS VIRUS by Ntungufhadzeni Maclaughlin Rathogwa Submitted in partial fulfillment of the requirements for the degree Master of Veterinary Science (MSc) in the Department of Veterinary Tropical Diseases Faculty of Veterinary Science University of Pretoria South Africa Supervisor: Prof Moritz van Vuuren Co-supervisor: Dr Melvyn Quan November, 2011 © University of Pretoria TABLE OF CONTENTS DEDICATION .......................................................................................................................................... II DECLARATION ..................................................................................................................................... III ACKNOWLEDGEMENTS ...................................................................................................................... IV ABBREVIATIONS ................................................................................................................................... V LIST OF FIGURES ................................................................................................................................ VII LIST OF TABLES ................................................................................................................................ VIII ABSTRACT ............................................................................................................................................ IX 1. GENERAL INTRODUCTION .........................................................................................................
    [Show full text]
  • Intracellular Trafficking of HBV Particles
    cells Review Intracellular Trafficking of HBV Particles Bingfu Jiang 1 and Eberhard Hildt 1,2,* 1 Department of Virology, Paul-Ehrlich-Institut, D-63225 Langen, Germany; [email protected] 2 German Center for Infection Research (DZIF), TTU Hepatitis, Marburg-Gießen-Langen, D63225 Langen, Germany * Correspondence: [email protected]; Tel.: +49-61-0377-2140 Received: 12 August 2020; Accepted: 2 September 2020; Published: 2 September 2020 Abstract: The human hepatitis B virus (HBV), that is causative for more than 240 million cases of chronic liver inflammation (hepatitis), is an enveloped virus with a partially double-stranded DNA genome. After virion uptake by receptor-mediated endocytosis, the viral nucleocapsid is transported towards the nuclear pore complex. In the nuclear basket, the nucleocapsid disassembles. The viral genome that is covalently linked to the viral polymerase, which harbors a bipartite NLS, is imported into the nucleus. Here, the partially double-stranded DNA genome is converted in a minichromosome-like structure, the covalently closed circular DNA (cccDNA). The DNA virus HBV replicates via a pregenomic RNA (pgRNA)-intermediate that is reverse transcribed into DNA. HBV-infected cells release apart from the infectious viral parrticle two forms of non-infectious subviral particles (spheres and filaments), which are assembled by the surface proteins but lack any capsid and nucleic acid. In addition, naked capsids are released by HBV replicating cells. Infectious viral particles and filaments are released via multivesicular bodies; spheres are secreted by the classic constitutive secretory pathway. The release of naked capsids is still not fully understood, autophagosomal processes are discussed. This review describes intracellular trafficking pathways involved in virus entry, morphogenesis and release of (sub)viral particles.
    [Show full text]
  • Changes to Virus Taxonomy 2004
    Arch Virol (2005) 150: 189–198 DOI 10.1007/s00705-004-0429-1 Changes to virus taxonomy 2004 M. A. Mayo (ICTV Secretary) Scottish Crop Research Institute, Invergowrie, Dundee, U.K. Received July 30, 2004; accepted September 25, 2004 Published online November 10, 2004 c Springer-Verlag 2004 This note presents a compilation of recent changes to virus taxonomy decided by voting by the ICTV membership following recommendations from the ICTV Executive Committee. The changes are presented in the Table as decisions promoted by the Subcommittees of the EC and are grouped according to the major hosts of the viruses involved. These new taxa will be presented in more detail in the 8th ICTV Report scheduled to be published near the end of 2004 (Fauquet et al., 2004). Fauquet, C.M., Mayo, M.A., Maniloff, J., Desselberger, U., and Ball, L.A. (eds) (2004). Virus Taxonomy, VIIIth Report of the ICTV. Elsevier/Academic Press, London, pp. 1258. Recent changes to virus taxonomy Viruses of vertebrates Family Arenaviridae • Designate Cupixi virus as a species in the genus Arenavirus • Designate Bear Canyon virus as a species in the genus Arenavirus • Designate Allpahuayo virus as a species in the genus Arenavirus Family Birnaviridae • Assign Blotched snakehead virus as an unassigned species in family Birnaviridae Family Circoviridae • Create a new genus (Anellovirus) with Torque teno virus as type species Family Coronaviridae • Recognize a new species Severe acute respiratory syndrome coronavirus in the genus Coro- navirus, family Coronaviridae, order Nidovirales
    [Show full text]
  • Human Rotavirus Structure, Specific Immunity And
    STUDIES OF HUMAN ROTAVIRUS CANDIDATE NON-REPLICATING VACCINES AND INNATE IMMUNITY IN A GNOTOBIOTIC PIG MODEL OF HUMAN ROTAVIRUS DISEASE DISSERTATION Presented as Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Ana María González, M.D * * * * The Ohio State University 2007 Dissertation Committee Approved by Distinguished University Professor Linda J. Saif, Adviser ________________________ Adviser Adjunct Assistant Professor Lijuan Yuan Graduate Program of Veterinary Preventive Associate Professor Kenneth W. Theil Medicine Professor Caroline Whitacre ABSTRACT Rotavirus is the major cause of severe dehydrating diarrhea in children and young infants worldwide. The mortality rates reach 600,000 annually, mainly in developing countries and vaccination is an important preventive measure. The first two objectives of my PhD research were to produce and test a combination of replicating and non-replicating human rotavirus (HRV) vaccines or non-replicating HRV vaccines in the gnotobiotic pig model to minimize or avoid the use of more reactogenic live HRV vaccines. The third objective was to assess the mucosal and systemic dendritic cell responses after RV infection because these responses are largely uncharacterized but are important in understanding immunity induced after infection and for design of vaccines. The neonatal gnotobiotic pig is susceptible to HRV for more than 8 weeks and their gnotobiotic status assures that wild type rotavirus infection does not occur during vaccination. Additionally gnotobiotic pigs are optimal for the study of innate immune responses to HRV in-vivo by excluding any confounding factors (e.g. commensal flora. other pathogens etc). For the first objective, gnotobiotic pigs were vaccinated priming with a peroral (PO) live attenuated human rotavirus (AttHRV) and boosting (2x) with a non-replicating 2/6 virus-like particles (VLPs) intranasally (IN) using ISCOM as adjuvant.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,096,585 B2 Shaw Et Al
    US009096585B2 (12) United States Patent (10) Patent No.: US 9,096,585 B2 Shaw et al. (45) Date of Patent: Aug. 4, 2015 (54) ANTIVIRAL COMPOUNDS AND USES (2013.01); C07D 413/10 (2013.01); C07D THEREOF 413/12 (2013.01); A61 K 3 1/5377 (2013.01); A61 K3I/55 (2013.01) (75) Inventors: Megan Shaw, New York, NY (US); (58) Field of Classification Search Hans-Heinrich Hoffmann, New York, CPC. A61K 31/4245; A61K31/5377; A61K31/55 NY (US); Adolfo Garcia-Sastre, New USPC .................................... 514/364, 217.1, 236.2 York, NY (US); Peter Palese, Leonia, NJ See application file for complete search history. US (US) (56) References Cited (73) Assignee: Icahn School of Medicine at Mount Sinai, New York, NY (US) U.S. PATENT DOCUMENTS 6,384,064 B2 5, 2002 Camden (*) Notice: Subject to any disclaimer, the term of this 8,278,342 B2 10/2012 Ricciardi patent is extended or adjusted under 35 Continued U.S.C. 154(b) by 210 days. (Continued) (21) Appl. No.: 13? 700,049 FOREIGN PATENT DOCUMENTS y x- - - 9 (22) PCT Filed1C Mavay 31,51, 2011 WO WO 2009,136979 A2 11/2009 OTHER PUBLICATIONS (86). PCT No.: PCT/US2011/038515 Chu et al. "Analysis of the endocytic pathway mediating the infec S371 (c)(1), tious entry of mosquito-borne flavivirus West Nile into Aedes (2), (4) Date: Feb. 14, 2013 albopictus mosquito (C6/36) cells.” Virology, 2006, vol. 349, pp. 463-475. (87) PCT Pub. No.: WO2011/150413 (Continued) PCT Pub. Date: Dec. 1, 2011 Primary Examiner — Shengjun Wang (65) Prior Publication Data (74) Attorney, Agent, or Firm — Jones Day US 2013/O137678A1 May 30, 2013 (57) ABSTRACT O O Described herein are Compounds, compositions comprising Related U.S.
    [Show full text]
  • Emerging Roles for Lipid Droplets in Immunity and Host-Pathogen Interactions
    CB28CH16-Valdivia ARI 5 September 2012 17:10 Emerging Roles for Lipid Droplets in Immunity and Host-Pathogen Interactions Hector Alex Saka and Raphael Valdivia Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, North Carolina 27710; email: [email protected] Annu. Rev. Cell Dev. Biol. 2012. 28:411–37 Keywords First published online as a Review in Advance on eicosanoids, interferon, autophagy May 11, 2012 The Annual Review of Cell and Developmental Abstract Biology is online at cellbio.annualreviews.org Lipid droplets (LDs) are neutral lipid storage organelles ubiquitous to Access provided by Duke University on 10/14/19. For personal use only. This article’s doi: eukaryotic cells. It is increasingly recognized that LDs interact exten- 10.1146/annurev-cellbio-092910-153958 sively with other organelles and that they perform functions beyond Annu. Rev. Cell Dev. Biol. 2012.28:411-437. Downloaded from www.annualreviews.org Copyright c 2012 by Annual Reviews. passive lipid storage and lipid homeostasis. One emerging function for All rights reserved LDs is the coordination of immune responses, as these organelles par- 1081-0706/12/1110-0411$20.00 ticipate in the generation of prostaglandins and leukotrienes, which are important inflammation mediators. Similarly, LDs are also beginning to be recognized as playing a role in interferon responses and in antigen cross presentation. Not surprisingly, there is emerging evidence that many pathogens, including hepatitis C and Dengue viruses, Chlamydia, and Mycobacterium, target LDs during infection either for nutritional purposes or as part of an anti-immunity strategy.
    [Show full text]
  • Runx1 Gene in Acute Myeloid Leukemia: Expression Level Signifcance and Impact on Clinical Features
    Runx1 Gene in Acute Myeloid Leukemia: Expression Level Signicance and Impact on Clinical Features Fadwa Said Abdelazim Mohamed ( [email protected] ) Cairo University Roxan E Shak National Cancer Institute, Cairo University Naglaa M. Hassan National Cancer Institute, Cairo University Research article Keywords: Acute myeloid leukemia, RUNX1, mutation, gene expression, Egypt Posted Date: April 7th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-20926/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/20 Abstract Background Acute myeloid leukemia represents the highest percentage of all adult acute leukemia variants. Runt-related transcription factor1 (RUNX1), a transcription factor with a known tumor suppressor function was recently reported as a tumor promotor in AML. We investigated the role of RUNX1 geneexpression levelin Egyptian AML patients and delineateits clinical signicance. Methods This study recruited 91 AML patients that were recently diagnosed at our hospital with 14 healthy age- and sex-matched donors of bone marrow transplantation unit. We measured RUNX1 gene expression level using reverse transcription–quantitative polymerase chain reaction. Results We found that RUNX1 gene expression level was signicantly higher compared to the control group (p < 0.001). Patients with FLT3 mutations had the higher expression level of RUNX1 (p=0.023). The male patients expressed signicantly higher level of RUNX1 (p=0.046). Conclusion The RUNX1 gene expression may serve as a diagnostic marker in Egyptian AML patients. Its relation to FLT3 may give clue that patients carrying this mutation may benet fromnew treatments that target RUNX1 in the future.
    [Show full text]
  • Lessons Learned from Ebola Virus
    membranes Review SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus Jordana Muñoz-Basagoiti 1,†, Daniel Perez-Zsolt 1,†, Jorge Carrillo 1 , Julià Blanco 1,2 , Bonaventura Clotet 1,2,3 and Nuria Izquierdo-Useros 1,* 1 IrsiCaixa AIDS Research Institute, Germans Trias I Pujol Research Institute (IGTP), Can Ruti Campus, 08916 Badalona, Spain; [email protected] (J.M.-B.); [email protected] (D.P.-Z.); [email protected] (J.C.); [email protected] (J.B.); [email protected] (B.C.) 2 Infectious Diseases and Immunity Department, Faculty of Medicine, University of Vic (UVic-UCC), 08500 Vic, Spain 3 Infectious Diseases Department, Germans Trias i Pujol Hospital, 08916 Badalona, Spain * Correspondence: [email protected] † These authors contribution is equally to this work. Abstract: Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS- CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, Citation: Muñoz-Basagoiti, J.; antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against Perez-Zsolt, D.; Carrillo, J.; Blanco, J.; the new coronavirus.
    [Show full text]
  • Mgr. Marie Vilánková
    www.novinky.cz www.rozhlas.cz VIRY Mgr. Marie Vilánková © ECC s.r.o. www.stefajir.cz Všechna práva vyhrazena Viry • Jejich zařazení do živé přírody • Virus jako informace • Jejich členění, • způsoby pronikání do lidského organismu, • nejčastější zdravotní problémy s nimi spojené • Možnosti řešení, včetně akutních infekcí, preparáty Joalis • Proč preparát Antivex je velmi důležitý © ECC s.r.o. Všechna práva vyhrazena Země • Životní prostředí – živé organismy - rostliny, živočichové… – tvořeny buňkami • Rostliny – počátek potravního řetězce, umí zachytávat sluneční energii a ukládat do chemických vazeb • Zvířata – zdroj potravy – rostliny nebo jiná zvířata • Houby a plísně – rozklad hmoty na základní prvky • Bakterie – také rozklad, velký význam v oběhu živin, prospěšné svazky s jinými organismy, mohou také škodit - Různé vztahy mezi organismy – boj o potravu, získání životního prostoru, přežití… © ECC s.r.o. Všechna práva vyhrazena Živé organismy • Živé organismy tvořeny buňkami – jednobuněčné (bakterie, prvoci, některé plísně), vícebuněčné • Buňka – tvořena ze specializovaných částí organel - cytoplasma, jádro, mitochondrie, endoplasmatické retikulum … • Buněčná membrána: dvojitá vrstva fosfolipidů s molekulami bílkovin – velmi důležité NENAsycené mastné kyseliny – VÝŽIVA!!! • Každá buňka – samostatný organismus – přijímá potravu, vylučuje, rozmnožuje se, reaguje na okolí, má nějakou fci -stavební produkuje stavební materiál (bílkoviny), transportní bariérová – přenáší částice přes bariéru, pohybová – natahuje a smršťuje se, signalizační © ECC s.r.o. Všechna práva vyhrazena Organismus = společnost buněk Soubor buněk = základní funkční jednotka • Propojeny pojivem – mezibuněčná hmota – produkt buněk vazivo, chrupavky, kosti, tekutiny • Tkáně: soubor buněk stejného typu (nervová, svalová, epitel...) • Orgány: skládají se z tkání, tvoří soustavy orgánů • Tělo: je složeno z buněk – 3,5 x 1013 buněk (lidí na Zemi 109) • Délka těla= 1,7 m, průměrná velikost buňky 10 - 20 mikrometru, měřítko 10-6 - člověk se dívá na svět z družice © ECC s.r.o.
    [Show full text]
  • A SARS-Cov-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
    A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing Supplementary Information Supplementary Discussion All SARS-CoV-2 protein and gene functions described in the subnetwork appendices, including the text below and the text found in the individual bait subnetworks, are based on the functions of homologous genes from other coronavirus species. These are mainly from SARS-CoV and MERS-CoV, but when available and applicable other related viruses were used to provide insight into function. The SARS-CoV-2 proteins and genes listed here were designed and researched based on the gene alignments provided by Chan et. al. 1 2020 .​ Though we are reasonably sure the genes here are well annotated, we want to note that not every ​ protein has been verified to be expressed or functional during SARS-CoV-2 infections, either in vitro or in vivo. ​ ​ In an effort to be as comprehensive and transparent as possible, we are reporting the sub-networks of these functionally unverified proteins along with the other SARS-CoV-2 proteins. In such cases, we have made notes within the text below, and on the corresponding subnetwork figures, and would advise that more caution be taken when examining these proteins and their molecular interactions. Due to practical limits in our sample preparation and data collection process, we were unable to generate data for proteins corresponding to Nsp3, Orf7b, and Nsp16. Therefore these three genes have been left out of the following literature review of the SARS-CoV-2 proteins and the protein-protein interactions (PPIs) identified in this study.
    [Show full text]