DOCSLIB.ORG

Antibody Correlates of Protection for Ebola Virus Infection: Effects of Mutations Within the Viral Glycoprotein on Immune Escape

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Antibody Correlates of Protection for Ebola Virus Infection: Effects of Mutations Within the Viral Glycoprotein on Immune Escape Antibody correlates of protection for Ebola virus infection: Effects of mutations within the viral glycoprotein on immune escape. Thesis submitted in accordance with the requirements of the University of Liverpool for the degree of Doctor in Philosophy by Kimberley Steeds. May 2019 Contents Abstract .................................................................................................................................... V Abbreviations ......................................................................................................................... VII Acknowledgments .................................................................................................................. XV Chapter 1 Introduction ............................................................................................................ 1 1.1 History of Ebola virus (EBOV) ......................................................................................... 1 1.1.1 Filovirus discovery ................................................................................................... 1 1.1.2 Ecology and transmission ........................................................................................ 4 1.1.3 Origin and evolutionary rate ................................................................................... 7 1.1.4 Clinical manifestations ............................................................................................ 9 1.1.5 Disease pathogenesis ............................................................................................ 10 1.2 Virology ........................................................................................................................ 14 1.2.1 Genome structure and organisation ..................................................................... 14 1.2.2 Virion structure and viral proteins ........................................................................ 15 1.2.3 EBOV GPs .............................................................................................................. 16 1.2.4 EBOV life cycle ....................................................................................................... 21 1.3 Immune response to EBOV .......................................................................................... 25 1.3.1 Innate immune response ...................................................................................... 25 1.3.2 Adaptive immune response .................................................................................. 26 1.3.3 Neutralising antibodies ......................................................................................... 32 1.4 Pseudotyped viruses .................................................................................................... 38 1.4.1 Retrovirus-based pseudotyped viruses ................................................................. 39 1.4.2 Rhabdovirus-based pseudotyped viruses ............................................................. 40 1.4.3 Neutralisation of pseudotyped viruses ................................................................. 43 1.4.4 Reverse genetics systems ..................................................................................... 44 1.5 EVD treatment and prevention .................................................................................... 49 1.5.1 Convalescent therapy ........................................................................................... 49 1.5.2 Monoclonal antibodies (mAbs) ............................................................................. 51 1.5.3 Vaccines ................................................................................................................ 54 1.5.4 Correlates of protection ........................................................................................ 60 1.5.5 Immune escape ..................................................................................................... 62 Chapter 2 Materials and Methods ......................................................................................... 64 2.1 Plasmids for generation of pseudotyped viruses......................................................... 64 2.1.1 Plasmids ................................................................................................................ 64 I 2.1.2 E. coli transformation ............................................................................................ 67 2.1.3 E. coli culture ......................................................................................................... 67 2.1.4 Plasmid DNA purification ...................................................................................... 67 2.1.5 Restriction enzyme digest ..................................................................................... 68 2.1.6 Separation of DNA fragments by agarose gel electrophoresis ............................. 68 2.1.7 Site-directed mutagenesis .................................................................................... 68 2.1.8 DNA sequencing .................................................................................................... 70 2.2 Cells for pseudotyped virus assays .............................................................................. 71 2.2.1 Cell culture ............................................................................................................ 71 2.3 Generation of pseudotyped viruses ............................................................................. 72 2.3.1 Production of EBOV GP pseudotyped lentiviruses by transfection ...................... 72 2.3.2 Production of EBOV GP pseudotyped VSV-G by transfection and infection ...... 73 2.3.3 Expansion of rVSV-G-Luc-VSV-G virus stock by transfection and infection ....... 74 2.4 Titration of pseudotyped viruses ................................................................................. 74 2.4.1 Pseudotyped lentivirus titration by luciferase assay ............................................ 74 2.4.2 Pseudotyped VSV-G titration by luciferase assay ............................................... 75 2.4.3 rVSV-G-Luc-VSV-G virus titration by plaque assay ............................................. 75 2.5 Neutralisation of pseudotyped viruses ........................................................................ 76 2.5.1 Human plasma samples ........................................................................................ 76 2.5.2 Pseudotyped lentivirus neutralisation assay ........................................................ 80 2.5.3 Pseudotyped VSV-G neutralisation assay ........................................................... 80 2.5.4 Statistical analysis ................................................................................................. 81 Chapter 3 Assessment of an EBOV GP pseudotyped lentivirus neutralisation assay ............ 82 3.1 Introduction ................................................................................................................. 82 3.1.1 Generation and quantification of pseudotyped lentiviruses ................................ 83 3.1.2 Neutralisation of pseudotyped viruses ................................................................. 84 3.1.3 Use of pseudotyped viruses as alternatives for infectious virus .......................... 84 3.2 Chapter aims ................................................................................................................ 85 3.3 Results .......................................................................................................................... 85 3.3.1 Preparation of plasmids for production of EBOV GP pseudotyped lentivirus ...... 85 3.3.2 Cell tropism of EBOV GP pseudotyped lentivirus ................................................. 86 3.3.3 Assessment of EBOV GP pseudotyped lentivirus input for neutralisation ........... 87 3.3.4 Neutralisation of EBOV GP pseudotyped lentivirus by EVD survivor plasma ....... 89 3.3.5 Reproducibility and correlation with live EBOV neutralisation ............................ 92 II 3.4 Discussion ..................................................................................................................... 94 3.4.1 Generation and quantification of EBOV GP pseudotyped lentivirus .................... 95 3.4.2 Neutralisation of EBOV GP pseudotyped lentivirus by EVD survivor plasma ....... 95 3.4.3 Suitability of EBOV GP pseudotyped lentivirus neutralisation assay for future use ....................................................................................................................................... 96 3.5 Conclusions .................................................................................................................. 98 Chapter 4 Assessment of an EBOV GP pseudotyped VSV neutralisation assay ..................... 99 4.1 Introduction ................................................................................................................. 99 4.1.1 Generation and quantification of pseudotyped VSVs .......................................... 99 4.1.2 Use of pseudotyped VSVs as alternatives for infectious virus ............................ 101 4.2 Chapter aims .............................................................................................................. 101 4.3 Results ........................................................................................................................ 102 4.3.1 rVSV-G-Luc-VSV-G virus expansion
Load more

Recommended publications
  • How Influenza Virus Uses Host Cell Pathways During Uncoating
    cells Review How Influenza Virus Uses Host Cell Pathways during Uncoating Etori Aguiar Moreira 1 , Yohei Yamauchi 2 and Patrick Matthias 1,3,* 1 Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; [email protected] 2 Faculty of Life Sciences, School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK; [email protected] 3 Faculty of Sciences, University of Basel, 4031 Basel, Switzerland * Correspondence: [email protected] Abstract: Influenza is a zoonotic respiratory disease of major public health interest due to its pan- demic potential, and a threat to animals and the human population. The influenza A virus genome consists of eight single-stranded RNA segments sequestered within a protein capsid and a lipid bilayer envelope. During host cell entry, cellular cues contribute to viral conformational changes that promote critical events such as fusion with late endosomes, capsid uncoating and viral genome release into the cytosol. In this focused review, we concisely describe the virus infection cycle and highlight the recent findings of host cell pathways and cytosolic proteins that assist influenza uncoating during host cell entry. Keywords: influenza; capsid uncoating; HDAC6; ubiquitin; EPS8; TNPO1; pandemic; M1; virus– host interaction Citation: Moreira, E.A.; Yamauchi, Y.; Matthias, P. How Influenza Virus Uses Host Cell Pathways during 1. Introduction Uncoating. Cells 2021, 10, 1722. Viruses are microscopic parasites that, unable to self-replicate, subvert a host cell https://doi.org/10.3390/ for their replication and propagation. Despite their apparent simplicity, they can cause cells10071722 severe diseases and even pose pandemic threats [1–3].
    [Show full text]
  • Ebolaviruses: New Roles for Old Proteins
    REVIEW Ebolaviruses: New roles for old proteins Diego Cantoni, Jeremy S. Rossman* School of Biosciences, University of Kent, Canterbury, United Kingdom * [email protected] Abstract In 2014, the world witnessed the largest Ebolavirus outbreak in recorded history. The subse- quent humanitarian effort spurred extensive research, significantly enhancing our under- standing of ebolavirus replication and pathogenicity. The main functions of each ebolavirus protein have been studied extensively since the discovery of the virus in 1976; however, the recent expansion of ebolavirus research has led to the discovery of new protein functions. a1111111111 These newly discovered roles are revealing new mechanisms of virus replication and patho- a1111111111 genicity, whilst enhancing our understanding of the broad functions of each ebolavirus viral a1111111111 a1111111111 protein (VP). Many of these new functions appear to be unrelated to the protein's primary a1111111111 function during virus replication. Such new functions range from bystander T-lymphocyte death caused by VP40-secreted exosomes to new roles for VP24 in viral particle formation. This review highlights the newly discovered roles of ebolavirus proteins in order to provide a more encompassing view of ebolavirus replication and pathogenicity. OPEN ACCESS Citation: Cantoni D, Rossman JS (2018) Ebolaviruses: New roles for old proteins. PLoS Negl Trop Dis 12(5): e0006349. https://doi.org/ Author summary 10.1371/journal.pntd.0006349 Between 2014 and 2016, West Africa experienced the largest Ebolavirus outbreak in Editor: Patricia V. Aguilar, University of Texas recorded history. The international containment effort spurred extensive research that is Medical Branch, UNITED STATES enhancing our understanding of ebolavirus replication and pathogenicity.
    [Show full text]
  • Eesha Acharya Project #1
    Eesha Acharya Project #1 Completed Project, Science, Health and Medical Measuring Vitamin C Levels in Cooked Foods Most people know that raw foods contain the most nutrients. However, many people prefer eating cooked foods. the problem is vitamin C is a water-soluble vitamin, so when foods are cooked they lose a lot of this essential nutrient. The purpose of this research is to determine which cooking method best retains the most vitamin C in vegetables. The raw vegetable vitamin C information will be compared to that of other cooking methods (grilling, boiling, and steaming) of that same vegetable. tomatoes, brussel sprouts, kale, bell peppers, broccoli, peas, and a tincture of iodine solution, 2-7% elemental iodine, will be used to test the vitamin C content. The food will be tested by mixing 10g of food to a starch-water mixture and straining the water. Drops of iodine will be added to the strained water until the solution turns black. The more iodine added, means the more vitamin C is in the food. Then the number of drops will be divided by 10g of food. This gives the drops per gram of food. This number will be multiplied by the factor. The drops per gram multiplied by the factor equals mg of vitamin C per gram of food This study is designed to help people consume more vitamin C. Many people in the United States have a vitamin C deficiency. Vitamin C is a key that prevents immune system deficiency and cardiovascular disease. So if a proper cooking method can be found, then people can consume more Vitamin C.
    [Show full text]
  • Downloads/ Hsp90interactors.Pdf), and Tend to Be Metastable, Being Rapidly Degraded Upon Hsp90 Inhibition
    viruses Review Chaperoning the Mononegavirales: Current Knowledge and Future Directions Victor Latorre †, Florian Mattenberger † and Ron Geller * Institute for Integrative Systems Biology (I2SysBio), Universitat de Valencia-CSIC, 46980 Valencia, Spain; [email protected] (V.L.); [email protected] (F.M.) * Correspondence: [email protected]; Tel.: +34-963-543-187 † These authors contributed equally to this work. Received: 16 November 2018; Accepted: 5 December 2018; Published: 8 December 2018 Abstract: The order Mononegavirales harbors numerous viruses of significant relevance to human health, including both established and emerging infections. Currently, vaccines are only available for a small subset of these viruses, and antiviral therapies remain limited. Being obligate cellular parasites, viruses must utilize the cellular machinery for their replication and spread. Therefore, targeting cellular pathways used by viruses can provide novel therapeutic approaches. One of the key challenges confronted by both hosts and viruses alike is the successful folding and maturation of proteins. In cells, this task is faced by cellular molecular chaperones, a group of conserved and abundant proteins that oversee protein folding and help maintain protein homeostasis. In this review, we summarize the current knowledge of how the Mononegavirales interact with cellular chaperones, highlight key gaps in our knowledge, and discuss the potential of chaperone inhibitors as antivirals. Keywords: Mononegavirales; chaperones; antivirals; Hsp70;
    [Show full text]
  • Structure of the Cleavage-Activated Prefusion Form of the Parainfluenza Virus 5 Fusion Protein
    Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein Brett D. Welcha,b,1, Yuanyuan Liua,b,1, Christopher A. Korsa,b, George P. Lesera,b, Theodore S. Jardetzkyc,2, and Robert A. Lamba,b,2 aHoward Hughes Medical Institute and bDepartment of Molecular Biosciences, Northwestern University, Evanston, IL 60208; and cDepartment of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305 Contributed by Robert A. Lamb, August 9, 2012 (sent for review June 28, 2012) The paramyxovirus parainfluenza virus 5 (PIV5) enters cells by refolding, resulting in formation of a trimeric coiled coil com- fusion of the viral envelope with the plasma membrane through posed of a heptad repeat A region that extends away from the the concerted action of the fusion (F) protein and the receptor viral membrane (18–20). binding protein hemagglutinin-neuraminidase. The F protein folds Peptide inhibitor studies and available atomic structures in- initially to form a trimeric metastable prefusion form that is trig- dicate that many of the key elements of this entry mechanism are gered to undergo large-scale irreversible conformational changes common to other class I viral fusion proteins, such as the hem- to form the trimeric postfusion conformation. It is thought that agglutinin (HA) of influenza virus, gp120/41 of HIV, S protein of F refolding couples the energy released with membrane fusion. severe acute respiratory syndrome coronavirus, and glycoprotein The F protein is synthesized as a precursor (F0) that must be (GP) of Ebola virus (reviewed in ref. 4). Although X-ray struc- cleaved by a host protease to form a biologically active molecule, tures of the six-helix bundle of many type I fusion proteins have F1,F2.
    [Show full text]
  • Gifc-2018 Book of Abstracts
    GIFC-2018 Giornate Italo-Francesi di Chimica Journées Franco-Italiennes de Chimie 16 – 18 April 2018 Grand Hotel Savoia Via Arsenale di Terra, 5 Genova BOOK OF ABSTRACTS ISBN: 978-88-94952-00-1 Gold Sponsors Silver Sponsors Patronages 2 3 Scientific Program 4 5 6 List of Posters (according to alphabetic order of presenting Authors) 1st session, Monday 16th April Num Cognome Nome Contatto Titolo Synthesis, purification and characterization of PO1 Aboudou Soioulata [email protected] antimicrobial peptides isolated from animal venoms [email protected] PO2 Ajmalghan Muthali Coverage dependent recombination mechanisms of hydrogen from niv-amu.fr tungsten surfaces via density functional theory Hybrid squaraine-silica nanoparticles as nir probes for biological PO3 Alberto Gabriele [email protected] applications: optimization of the photoemission performances Synthesis of doped metal oxide nanocrystals for solution-processed PO4 Alkarsifi Riva [email protected] interfacial layers in organic solar cells PO5 Anceschi Anastasia [email protected] Maltodextrins nanosponges as precursor for porous carbon materials [email protected] PO7 Arnodo Davide First racemic total synthesis of heliolactone .it [email protected]. PO8 Azzi Emanuele Synthesis of boronated analogue of curcumin as potential therapeutical it agents for alzheimer’s disease Study of Nanobiomaterials with Bio-based Antioxidants: Interaction of PO9 Barzan Giulia Sci piem Polyphenol Molecules with Hydroxyapatite and Silica Luigi Methotrexate loaded solid lipid nanoparticles: protein functionalization to PO10 Battaglia [email protected] Sebastiano improve brain biodistribution [email protected] PO11 Begni Federico On the adsorption of toluene on porous materials with different chemical m composition Synthesischaracterization of activated carbon from modified banana peels PO12 Ben Khalifa Eya [email protected] for hexavalent chromium adsorption [email protected] PO13 Benvenuti Martino The maturation of the co-dehydrogenase from thermococcus sp.
    [Show full text]
  • Acetylcholine Receptors 61 Acid Blob Activator 321 Acquired Immune
    WBVINDEX 6/27/03 11:39 PM Page 428 Index Note: page numbers in italics refer to figures, those in bold refer to tables. Illustrations in the Plate Section are indicated by Plate number. acetylcholine receptors 61 AIDS 5, 40, 89 Fc region 168, 172, 173, 174, acid blob activator 321 development 332 175–6 acquired immune deficiency enabling factors for disease 386 measurement of antiviral 91–5 syndrome see AIDS immune dysfunction 86–7 structure 167–8 actin fibers, HSV-induced changes impact 383, 384–5 antibody–antigen complexes 93–4 134, 135 Kaposi’s sarcoma 332 bacterial proteins for detection/ acycloguanosine (acG) 107, 108 protease inhibitors 235 isolation 173–4, 174–5 acyclovir 107, 108 T cell destruction 372 antigen(s), viral 18, 39, 77 adeno-associated virus (AAV) see also HIV antibodies bound to 172–3 305–6 alfalfa looper virus (AcNPV) 333, internalization 85 gene delivery 388 334 processing 82–3, 83–4 latent infection 306, 389 algal viruses 351–2 vaccine production 101 cyclic adenosine monophosphate Alzheimer’s disease, gene therapy antigen presentation (cAMP) 199 389 to immune reactive cells 80–6 adenovirus 23, 38 amantadine 108–9 local immunity 82 capsid amino acid epitopes 78, 79, 81 antigen presenting cells (APCs) 77, proteins 149, 150, 151 aminopterin 170 78 structure 301 cAMP receptor protein (CRP) immune response initiation DNA 287 199 82–5 replication 301–3 amplification, viral 24 professional 83 E1A gene 301, 302 aneuploidy 129 antigenic determinants 78, 81 E1B protein 301, 302 animal cells 11, 12 antigenic drift 88 E2 region
    [Show full text]
  • Docking-Based Screening of Cell-Penetrating Peptides With
    Chapter Docking-Based Screening of Cell-Penetrating Peptides with Antiviral Features and Ebola Virus Proteins as a Drug Discovery Approach to Develop a Treatment for Ebola Virus Disease Ehsan Raoufi, Bahar Bahramimeimandi, Mahsa Darestanifarahani, Fatemeh Hosseini, Mohammad Salehi-Shadkami, Hossein Raoufi and Reza Afzalipour Abstract Ebola drug discovery continues to be challenging as yet. Proteins of the virus should be targeted at the relevant biologically active site for drug or inhibitor bind- ing to be effective. In this regard, by considering the important role of Ebola virus proteins in the viral mechanisms of this viral disease, the Ebola proteins are selected as our drug targets in this study. The discovery of novel therapeutic molecules or peptides will be highly expensive; therefore, we attempted to identify possible anti- gens of EBOV proteins by conducting docking-based screening of cell penetrating peptides (CPPs) that have antiviral potential features utilizing Hex software version 8.0.0. The E-value scores obtained in this research were very much higher than the previously reported docking studies. CPPs that possess suitable interaction with the targets would be specified as promising candidates for further in vitro and in vivo examination aimed at developing new drugs for Ebola infection treatment. Keywords: bioinformatics, protein-peptide interactions, biological targets, drug development, HEX software, biological computation, drug design, CPP 1. Introduction Ebola virus disease or EVD is a frequently fatal disease caused by a member of the Filoviridae family known as Ebola virus (EBOV) [1]. The pathogen was initially discovered in Africa in 1976 and then leaded to two serious outbreaks including the 2013–2016 outbreak of EVD in Western Africa that infected 28,652 people with 1 Viral Outbreaks 11,323 documented deaths; and 2018–2020 outbreak of EVD in the Democratic Republic of the Congo that affected 3481 people with 2299 documented deaths [2].
    [Show full text]
  • Development and Validation of a Novel Dual Luciferase Reporter Gene Assay to Quantify Ebola Virus VP24 Inhibition of IFN Signaling
    viruses Article Development and Validation of a Novel Dual Luciferase Reporter Gene Assay to Quantify Ebola Virus VP24 Inhibition of IFN Signaling Elisa Fanunza 1 ID , Aldo Frau 1, Marco Sgarbanti 2, Roberto Orsatti 2, Angela Corona 1 ID and Enzo Tramontano 1,3,* ID 1 Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy; [email protected] (E.F.); [email protected] (A.F.); [email protected] (A.C.) 2 Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy; [email protected] (M.S.); [email protected] (R.O.) 3 Genetics and Biomedical Research Institute, National Research Council, 09042 Monserrato, Italy * Correspondence: [email protected]; Tel.: +39-070-6754538 Received: 11 January 2018; Accepted: 22 February 2018; Published: 24 February 2018 Abstract: The interferon (IFN) system is the first line of defense against viral infections. Evasion of IFN signaling by Ebola viral protein 24 (VP24) is a critical event in the pathogenesis of the infection and, hence, VP24 is a potential target for drug development. Since no drugs target VP24, the identification of molecules able to inhibit VP24, restoring and possibly enhancing the IFN response, is a goal of concern. Accordingly, we developed a dual signal firefly and Renilla luciferase cell-based drug screening assay able to quantify IFN-mediated induction of Interferon Stimulated Genes (ISGs) and its inhibition by VP24. Human Embryonic Kidney 293T (HEK293T) cells were transiently transfected with a luciferase reporter gene construct driven by the promoter of ISGs, Interferon-Stimulated Response Element (ISRE). Stimulation of cells with IFN-α activated the IFN cascade leading to the expression of ISRE.
    [Show full text]
  • Homology Modeling Active Site Predictive of VP24 Protein Involved in Ebola Virus Savita Patil1, Amol Thete2,Jyoti Kondhalkar3 Pooja Surwase4 Sweta Dhumal5
    GSJ: Volume 7, Issue 10, October 2019 ISSN 2320-9186 828 GSJ: Volume 7, Issue 10, October 2019, Online: ISSN 2320-9186 www.globalscientificjournal.com Homology modeling active site predictive of VP24 protein involved in Ebola Virus 1 2 3 4 5 Savita Patil , Amol thete ,Jyoti Kondhalkar Pooja Surwase Sweta dhumal . Bioreinventors LLP.PVT.LTD, department of biotechnology, [email protected] Abstract: Ebola is a single stranded RNA virus which has a filamentous structure and belongs to family of RNA virus called Filoviridae and genus Ebolavirus. Ebola virus causes severe hemorrhagic fever and is therefore a fatal disease in humans and non-human primates. Ebola viral protein (VP24) is a secondary matrix protein which has various roles in virulence of virus. VP24 interferes with the interferon signaling pathway by binding to karyopherin-α and blocking the Signal Transducers and Activators of Transcription (STAT-1) signaling pathway. In the present study we analyze protein sequence and predicted the 3 dimensional structure of VP24 protein using various bioinformatics tools. And we have also predicted the active/binding sites for the protein. These sites can be further use for the drug designing purpose for VP24 protein. It is thus involved in packaging of virus and in turn plays an important role in virulence. Since VP24 is present on the surface of viral envelope that has an affinity for plasma membrane. This protein is also essential for the replication of other proteins of virus as was suggested by Mateo et al and because of these reasons VP24 protein was selected for this study In this study Three dimensional structure predicted and validated by Swiss model and Ramachandran plot respectively.
    [Show full text]
  • Evolutionary Trends in Viral Pathogens Within and Between Outbreaks
    EVOLUTIONARY TRENDS IN VIRAL PATHOGENS WITHIN AND BETWEEN OUTBREAKS A dissertation submitted to Kent State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy by Mary E. Saha December 2017 © Copyright All rights reserved Except for previously published materials Dissertation written by Mary E Saha B.S., University of Akron, 2008 Ph.D., Kent State University, 2017 Approved by _Dr. Helen Piontkivska___________ Chair, Doctoral Dissertation Committee _Dr. Gary Koski_________________ Members, Doctoral Dissertation Committee _Dr. Christopher Woolverton_______ _Dr. Tara Smith_________________ _Dr. Walter Hoeh________________ _Dr. Gail Fraizer_________________ Accepted by __Dr. Laura Leff________________ Chair, Department of Biology __Dr. James Blank_______________ Dean, College of Arts and Sciences Table of Contents LIST OF FIGURES ......................................................................................................... V LIST OF TABLES ........................................................................................................ VII ACKNOWLEDGEMENTS ........................................................................................ VIII CHAPTER 1: INTRODUCTION .................................................................................... 1 1.1 RNA viruses .............................................................................................................. 1 1.2 Influenza A...................................................................................................................
    [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]