The role of nonsense-mediated mRNA decay on host defense system and influenza virus replication

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1. Verfasser: Tran, Vu Quynh Giao 1990- (VerfasserIn)
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Sprache:English
Veröffentlicht: Münster 2020
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adam_text LIST OF CONTENTS LIST OF FIGURES .............................................................................................................................. ILL LIST OF TABLES .............................................................................................................................. IV ABBREVIATIONS .............................................................................................................................. V 1. INTRODUCTION ........................................................................................................................... 1 1.1 INFLUENZA AND ITS CHARACTERISTICS ....................................................................................... 1 1.1.1 CLASSIFICATION AND BIOLOGY OF INFLUENZA A VIRUS ......................................................... 1 1.1.2 VIRUS STRUCTURE AND PROTEINS ...................................................................................... 3 1.1.3 REPLICATION CYCLE ...................................................................................................... 5 1.2 INFLUENZA VIRUS INDUCES INNATE IMMUNE RESPONSES IN HOST CELLS ..................................... 9 1.2.1 PATHOGEN RECOGNITION RECEPTORS FOR IAV ................................................................... 9 1.2.2 CYTOKINES ............................................................................................................... 11 1.2.3 POTENTIAL FOR IMMUNOPATHOLOGICAL ACTION OF THE INNATE IMMUNE RESPONSE ................ 13 1.3 POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION IN INNATE IMMUNITY ........................... 13 1.3.1 ALTERNATIVE SPLICING AND POLYADENYLATION IN INNATE IMMUNITY .................................... 14 1.3.2 MRNA STABILITY IN INNATE IMMUNITY ........................................................................... 15 1.3.3 TRANSLATION EVENTS REGULATE THE INNATE IMMUNE RESPONSE ....................................... 22 1.4 THE RELATION BETWEEN THE CELLULAR NONSENSE-MEDIATED MRNA DECAY AND VRNAS ........ 23 1.4.1 VRNAS CAN BE SUBSTRATES FOR NMD ........................................................................ 23 1.4.2 VIRUSES HAVE THE CAPACITY TO MANIPULATE NMD ACTIVITY ............................................ 24 1.5 AIM OF THIS STUDY ............................................................................................................ 25 2. MATERIALS AND METHODS ....................................................................................................... 27 2.1 MATERIALS ....................................................................................................................... 27 2.1.1 COMMON MATERIALS ................................................................................................. 27 2.1.2 MEDIA AND BUFFERS .................................................................................................. 36 2.1.3 HARDWARE AND EQUIPMENT ....................................................................................... 39 2.1.4 SOFTWARE ................................................................................................................. 40 2.2 METHODS ........................................................................................................................ 40 2.2.1 CELL CULTURE METHODS ............................................................................................... 40 2.2.2 CRYOCONSERVATION OF CELLS ...................................................................................... 41 2.2.3 CELL TREATMENTS ....................................................................................................... 41 2.2.4 VIROLOGICAL METHODS ................................................................................................ 43 LIST OF CONTENTS 2.2.5 MOLECULAR BIOLOGICAL METHODS - NUCLEIC ACID ........................................................ 46 2.2.6 MOLECULAR BIOLOGY METHODS - PROTEINS .................................................................. 50 3. RESULTS ................................................................................................................................ 53 3.1 FUNCTIONS OF MRNA STABILITY REGULATING PROTEINS IN INNATE IMMUNE RESPONSES DURING INFLUENZA A VIRUS INFECTIONS ...................................................................................................... 53 3.1.1 SCREENINGS FOR EXPRESSION PROFILES OF MRNA STABILITY REGULATING PROTEINS DURING INFLUENZA A VIRUS INFECTIONS OR PAMP STIMULATION (VRNA) ..................................................... 53 3.1.2 THE DOWNSHIFT IN TRANSCRIPTIONAL LEVELS OF NMD PROTEINS UPON INFLUENZA INFECTION IS MORE PROMINENT THAN FOR UNRELATED CELLULAR CONTROL GENES .................................................... 58 3.1.3 PHARMACOLOGICAL BLOCKAGE OF NMD AFFECTS INNATE IMMUNE RESPONSES .................. 60 3.1.4 THE TRANSCRIPTS OF INNATE IMMUNE GENES ARE NOT AFFECTED BY THE SILENCING OF NMD COMPONENT EXPRESSIONS ........................................................................................................ 65 3.1.5 MANIPULATING THE EXPRESSION OF UPF1 DOES NOT AFFECT THE PRO-INFLAMMATORY RESPONSE .............................................................................................................................. 67 3.2 THE INFLUENCE OF THE NMD PATHWAY IN VIRUS REPLICATION ................................................. 73 3.2.1 SILENCING THE EXPRESSION OF UPF1 DOES NOT APPARENTLY RESULT IN ALTERED IAV REPLICATION ............................................................................................................................. 74 3.2.2 KNOCKDOWN OF CRITICAL NMD PROTEINS DOES NOT AFFECT IAV H1N1 REPLICATION .......... 78 3.2.3 KNOCKDOWN OF NMD COMPONENTS DOES NOT INFLUENCE THE REPLICATION OF DIFFERENT SUBTYPES OF IAV .................................................................................................................... 82 3.2.4 BLOCKAGE OF THE NMD MACHINERY BY A PHARMACOLOGICAL INHIBITOR DOES NOT INFLUENCE IAV REPLICATION ...................................................................................................................... 84 3.2.5 DOWNREGULATION OF NMD FACTORS BY RNAI DOES NOT AFFECT RESPIRATORY SYNCYTIAL VIRUS (RSV) REPLICATION .................................................................................................................. 86 4. DISCUSSION .......................................................................................................................... 90 4.1 THE INTERPLAY BETWEEN INFLUENZA VIRUSES AND INNATE IMMUNE RESPONSES ...................... 90 4.2 IAV INFECTIONS MANIPULATE THE EXPRESSION OF MRNA DECAY PROTEINS AND NMD FACTORS .92 4.3 THE INFLUENCE OF THE NMD PATHWAY ON INNATE IMMUNE RESPONSE AFTER INFLUENZA VIRUS INFECTIONS .................................................................................................................................. 94 4.4 THE ROLE OF NMD FACTORS IN INFLUENZA VIRUS REPLICATION ................................................... 96 5. SUMMARY ............................................................................................................................ 102 6. REFERENCES ......................................................................................................................... 103 7. ACKNOWLEDGEMENT ............................................................................................................ 122 8. LEBENSLAUF ......................................................................................................................... 124 9. EIDESSTATTLICHE ERKLARUNG ................................................................................................ 126 II
adam_txt LIST OF CONTENTS LIST OF FIGURES . ILL LIST OF TABLES . IV ABBREVIATIONS . V 1. INTRODUCTION . 1 1.1 INFLUENZA AND ITS CHARACTERISTICS . 1 1.1.1 CLASSIFICATION AND BIOLOGY OF INFLUENZA A VIRUS . 1 1.1.2 VIRUS STRUCTURE AND PROTEINS . 3 1.1.3 REPLICATION CYCLE . 5 1.2 INFLUENZA VIRUS INDUCES INNATE IMMUNE RESPONSES IN HOST CELLS . 9 1.2.1 PATHOGEN RECOGNITION RECEPTORS FOR IAV . 9 1.2.2 CYTOKINES . 11 1.2.3 POTENTIAL FOR IMMUNOPATHOLOGICAL ACTION OF THE INNATE IMMUNE RESPONSE . 13 1.3 POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION IN INNATE IMMUNITY . 13 1.3.1 ALTERNATIVE SPLICING AND POLYADENYLATION IN INNATE IMMUNITY . 14 1.3.2 MRNA STABILITY IN INNATE IMMUNITY . 15 1.3.3 TRANSLATION EVENTS REGULATE THE INNATE IMMUNE RESPONSE . 22 1.4 THE RELATION BETWEEN THE CELLULAR NONSENSE-MEDIATED MRNA DECAY AND VRNAS . 23 1.4.1 VRNAS CAN BE SUBSTRATES FOR NMD . 23 1.4.2 VIRUSES HAVE THE CAPACITY TO MANIPULATE NMD ACTIVITY . 24 1.5 AIM OF THIS STUDY . 25 2. MATERIALS AND METHODS . 27 2.1 MATERIALS . 27 2.1.1 COMMON MATERIALS . 27 2.1.2 MEDIA AND BUFFERS . 36 2.1.3 HARDWARE AND EQUIPMENT . 39 2.1.4 SOFTWARE . 40 2.2 METHODS . 40 2.2.1 CELL CULTURE METHODS . 40 2.2.2 CRYOCONSERVATION OF CELLS . 41 2.2.3 CELL TREATMENTS . 41 2.2.4 VIROLOGICAL METHODS . 43 LIST OF CONTENTS 2.2.5 MOLECULAR BIOLOGICAL METHODS - NUCLEIC ACID . 46 2.2.6 MOLECULAR BIOLOGY METHODS - PROTEINS . 50 3. RESULTS . 53 3.1 FUNCTIONS OF MRNA STABILITY REGULATING PROTEINS IN INNATE IMMUNE RESPONSES DURING INFLUENZA A VIRUS INFECTIONS . 53 3.1.1 SCREENINGS FOR EXPRESSION PROFILES OF MRNA STABILITY REGULATING PROTEINS DURING INFLUENZA A VIRUS INFECTIONS OR PAMP STIMULATION (VRNA) . 53 3.1.2 THE DOWNSHIFT IN TRANSCRIPTIONAL LEVELS OF NMD PROTEINS UPON INFLUENZA INFECTION IS MORE PROMINENT THAN FOR UNRELATED CELLULAR CONTROL GENES . 58 3.1.3 PHARMACOLOGICAL BLOCKAGE OF NMD AFFECTS INNATE IMMUNE RESPONSES . 60 3.1.4 THE TRANSCRIPTS OF INNATE IMMUNE GENES ARE NOT AFFECTED BY THE SILENCING OF NMD COMPONENT EXPRESSIONS . 65 3.1.5 MANIPULATING THE EXPRESSION OF UPF1 DOES NOT AFFECT THE PRO-INFLAMMATORY RESPONSE . 67 3.2 THE INFLUENCE OF THE NMD PATHWAY IN VIRUS REPLICATION . 73 3.2.1 SILENCING THE EXPRESSION OF UPF1 DOES NOT APPARENTLY RESULT IN ALTERED IAV REPLICATION . 74 3.2.2 KNOCKDOWN OF CRITICAL NMD PROTEINS DOES NOT AFFECT IAV H1N1 REPLICATION . 78 3.2.3 KNOCKDOWN OF NMD COMPONENTS DOES NOT INFLUENCE THE REPLICATION OF DIFFERENT SUBTYPES OF IAV . 82 3.2.4 BLOCKAGE OF THE NMD MACHINERY BY A PHARMACOLOGICAL INHIBITOR DOES NOT INFLUENCE IAV REPLICATION . 84 3.2.5 DOWNREGULATION OF NMD FACTORS BY RNAI DOES NOT AFFECT RESPIRATORY SYNCYTIAL VIRUS (RSV) REPLICATION . 86 4. DISCUSSION . 90 4.1 THE INTERPLAY BETWEEN INFLUENZA VIRUSES AND INNATE IMMUNE RESPONSES . 90 4.2 IAV INFECTIONS MANIPULATE THE EXPRESSION OF MRNA DECAY PROTEINS AND NMD FACTORS .92 4.3 THE INFLUENCE OF THE NMD PATHWAY ON INNATE IMMUNE RESPONSE AFTER INFLUENZA VIRUS INFECTIONS . 94 4.4 THE ROLE OF NMD FACTORS IN INFLUENZA VIRUS REPLICATION . 96 5. SUMMARY . 102 6. REFERENCES . 103 7. ACKNOWLEDGEMENT . 122 8. LEBENSLAUF . 124 9. EIDESSTATTLICHE ERKLARUNG . 126 II
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spelling Tran, Vu Quynh Giao 1990- Verfasser (DE-588)121197958X aut
The role of nonsense-mediated mRNA decay on host defense system and influenza virus replication vorgelegt von Vu Quynh Giao Tran
Münster 2020
VIII, 126 Blatt Illustrationen 30 cm
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Dissertation Westfälische Wilhelms-Universyität Münster 2020 Beschränkt für den Austausch
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spellingShingle Tran, Vu Quynh Giao 1990-
The role of nonsense-mediated mRNA decay on host defense system and influenza virus replication
subject_GND (DE-588)4113937-9
title The role of nonsense-mediated mRNA decay on host defense system and influenza virus replication
title_auth The role of nonsense-mediated mRNA decay on host defense system and influenza virus replication
title_exact_search The role of nonsense-mediated mRNA decay on host defense system and influenza virus replication
title_exact_search_txtP ˜Theœ role of nonsense-mediated mRNA decay on host defense system and influenza virus replication
title_full The role of nonsense-mediated mRNA decay on host defense system and influenza virus replication vorgelegt von Vu Quynh Giao Tran
title_fullStr The role of nonsense-mediated mRNA decay on host defense system and influenza virus replication vorgelegt von Vu Quynh Giao Tran
title_full_unstemmed The role of nonsense-mediated mRNA decay on host defense system and influenza virus replication vorgelegt von Vu Quynh Giao Tran
title_short The role of nonsense-mediated mRNA decay on host defense system and influenza virus replication
title_sort the role of nonsense mediated mrna decay on host defense system and influenza virus replication
topic_facet Hochschulschrift
url https://d-nb.info/1211744434/04
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