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Role of Mimivirus Collagen in Rheumatoid Arthritis

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Role of Mimivirus Collagen in Rheumatoid Arthritis Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2013 Role of mimivirus collagen in rheumatoid arthritis Shah, Nikunj Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-93001 Dissertation Originally published at: Shah, Nikunj. Role of mimivirus collagen in rheumatoid arthritis. 2013, University of Zurich, Faculty of Science. Role of Mimivirus Collagen in Rheumatoid Arthritis Dissertation zur Erlangung der naturwissenschaftlichen Doktorwürde (Dr. sc. nat.) vorgelegt der Mathematisch-naturwissenschaftlichen Fakultät der Universität Zürich von Nikunj Shah aus Indien Promotionskomitee Prof. Dr. Thierry Hennet (Vorsitz) PD. Dr. Lubor Borsig Prof. Dr. Matthias Baumgartner PD. Dr. Patricie Burda Zürich, 2013 Table of Contents Summary ........................................................................................................................................... 5 Zusammenfassung ....................................................................................................................... 7 Abbreviations ................................................................................................................................. 9 Introduction ................................................................................................................................. 10 Acanthamoeba polyphaga mimivirus ........................................................................................ 10 Discovery ................................................................................................................................................ 10 Classification ......................................................................................................................................... 11 Nucleo-Cytoplasmic Large DNA Virus (NCLDV) ...................................................................... 11 Genome complexity of mimivirus ................................................................................................. 17 Structure of mimivirus particles ................................................................................................... 19 Mimivirus replication ........................................................................................................................ 20 Ever increasing family of Mimiviridae ......................................................................................... 22 Origin and evolution of giant viruses .......................................................................................... 24 Prevalence of giant viruses in environment ............................................................................. 26 Potential pathogenicity of mimivirus in humans .................................................................... 26 (Dis)Similarities between human and mimivirus collagens .............................................. 28 Rheumatoid Arthritis ......................................................................................................................... 35 Introduction to autoimmunity ....................................................................................................... 35 Immune tolerance ............................................................................................................................... 35 Causes of rheumatoid arthritis ...................................................................................................... 42 Pathogenesis, immune regulations and progression of rheumatoid arthritis ............ 46 Treatment strategies towards rheumatoid arthritis ............................................................. 48 Animal models of rheumatoid arthritis ...................................................................................... 49 Aims and objectives ............................................................................................................................ 53 Materials and Methods ........................................................................................................... 54 Ethics statement .................................................................................................................................. 54 Mimivirus infection ............................................................................................................................ 54 Mimivirus protein preparation ...................................................................................................... 54 CIA mouse model ................................................................................................................................. 54 Anti-CII antibodies .............................................................................................................................. 55 Histology ................................................................................................................................................. 55 Recall assay ............................................................................................................................................ 55 In vivo imaging ...................................................................................................................................... 56 Anti-mimivirus ELISA ........................................................................................................................ 56 Immunoprecipitation of mimivirus proteins ........................................................................... 56 Cloning, bacterial expression and purification of recombinant proteins ...................... 57 Western blotting .................................................................................................................................. 58 Statistical analysis ............................................................................................................................... 58 Isolation of giant viruses from environment ............................................................................ 59 Results............................................................................................................................................. 61 Mimivirus proteins promotes arthritis in mice ................................................................... 61 Joint inflammation in mice immunized with mimivirus proteins .................................... 61 Localization of joint inflammation in joint articular tissues .............................................. 63 Breakage of immune tolerance in immunized mice .............................................................. 65 Immunity to mimivirus in humans ............................................................................................. 67 Exposure to mimivirus in humans ................................................................................................ 67 Specific mimivirus proteins recognized by human sera ...................................................... 70 Isolation of giant viruses from environment ........................................................................ 78 Discussion ..................................................................................................................................... 85 Should we worry about mimivirus? ............................................................................................. 87 Microbes and molecular mimicry ................................................................................................. 89 Future directions ................................................................................................................................. 92 Conclusions ............................................................................................................................................ 93 References .................................................................................................................................... 94 Appendix ...................................................................................................................................... 106 Acknowledgments .................................................................................................................. 138 Curriculum Vitae ..................................................................................................................... 140 Summary Giant viruses with genomes larger than several bacterial genomes have been extensively described in the past decade. These giant viruses express proteins previously not identified in any viruses and thus giant viruses have garnered widespread evolutionary and biological importance. The giant mimivirus is an amoeba- associated virus that replicates in the ubiquitously present amoeba Acanthamoeba polyphaga. Sequence analysis revealed that mimivirus harbours a linear double stranded DNA genome of ~1.2 Mbp making mimivirus the third largest viral genome known to mankind. Mimivirus exhibits many features that have never been identified in a virus before, such as genes for aminoacyl-tRNA synthetases, DNA repair mechanisms, and enzymes related to novel metabolic pathways. Interestingly, mimivirus also harbours seven open reading frames encoding collagen-like proteins sharing structural similarity with collagen proteins in animals. Infections with microbes having similar immunogenic epitopes as self-proteins have
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