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dc.contributor.authorPuttaraksa, Kanoktip
dc.date.accessioned2017-06-06T06:58:18Z
dc.date.available2017-06-06T06:58:18Z
dc.date.issued2017
dc.identifier.isbn978-951-39-7115-1
dc.identifier.otheroai:jykdok.linneanet.fi:1703013
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/54311
dc.description.abstractIt is known that viral infections can cause acute, chronic, and autoimmune diseases (ADs). However, the mechanism of how a persistent viral infection contributes to ADs remains still unclear. In this thesis, pathological and immunological aspects of how common viruses can initiate autoimmunity were investigated, and human parvovirus B19 (B19V) was employed as a model virus. B19V non-structural protein 1 (NS1), a superfamily 3 (SF3) helicase, initiated DNA damage resulting in cellular apoptosis. The apoptotic bodies (ApoBods) induced by B19V NS1 were purified and characterized. These ApoBods contained viral NS1 proteins with modified autoimmune-associated self-antigens, e.g. DNA, Smith, Apolipoprotein H, and histone 4. Subsequently, in vitro B19V-induced ApoBods were phagocytized by macrophages that produced pro- inflammatory cytokines and chemokines such as sICAM-1, IL-8, TNF-Į, and IFN-Ȗ. Furthermore in vivo, the properties of viral-induced ApoBods causing immune responses were examined by immunization of these viral ApoBods to the non- autoimmune mice. Pathogenesis of systemic lupus erythematosus (SLE)-like disease was assessed in mice by observing the production of autoantibodies against dsDNA, as well as inflammation and destruction in major organs. Glomerulonephritis was also identified within the mice as an indicator of lupus nephritis. It is speculated that epitope spreading and cryptic epitope are the key mechanisms to activate immune reactions leading to autoimmunity. Moreover, the clinical research indicated that antibodies against viral ApoBods, a novel antigen, were detected in chronic B19V infection and SLE-like patients. We hypothesize that the components of ApoBods, such as DNA and Smith, were the influential targets for stimulating autoimmunity in the host. Ineffective phagocytosis of viral-induced ApoBods could enable the release of viral proteins and self-antigens that participate in the collapse of immunological tolerance. In summary, ApoBods created by chronic viral infections can participate in the destruction of self-tolerance.
dc.format.extent1 verkkoaineisto (179 sivua) : kuvitettu
dc.language.isoeng
dc.publisherUniversity of Jyväskylä
dc.relation.ispartofseriesJyväskylä studies in biological and environmental science
dc.relation.isversionofJulkaistu myös painettuna.
dc.subject.otherself-antigens
dc.subject.othernon-structural protein 1
dc.subject.otherhuman parvovirus B19
dc.subject.otherautoimmunity
dc.subject.otherautoantibodies
dc.subject.otherapoptotic bodies
dc.subject.otherapoptosis
dc.titlePathogenic mechanisms of how human parvovirus breaks self-tolerance
dc.typeDiss.fi
dc.identifier.urnURN:ISBN:978-951-39-7115-1
dc.type.dcmitypeTexten
dc.type.ontasotVäitöskirjafi
dc.type.ontasotDoctoral dissertationen
dc.contributor.tiedekuntaMatemaattis-luonnontieteellinen tiedekuntafi
dc.contributor.yliopistoUniversity of Jyväskyläen
dc.contributor.yliopistoJyväskylän yliopistofi
dc.contributor.oppiaineSolu- ja molekyylibiologiafi
dc.relation.issn1456-9701
dc.relation.numberinseries330
dc.rights.accesslevelopenAccessfi
dc.subject.ysovirukset
dc.subject.ysoparvovirukset
dc.subject.ysoinfektiot
dc.subject.ysopatogeneesi
dc.subject.ysoimmunologia
dc.subject.ysoautoimmuniteetti
dc.subject.ysoohjelmoitunut solukuolema
dc.subject.ysovasta-aineet
dc.subject.ysoautovasta-aineet
dc.subject.ysoantigeenit


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