Cell biology of canine parvovirus entry

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dc.contributor.author Suikkanen, Sanna
dc.date.accessioned 2008-01-09T12:52:42Z
dc.date.available 2008-01-09T12:52:42Z
dc.date.issued 2003
dc.identifier.isbn 951-39-1785-1
dc.identifier.uri http://urn.fi/URN:ISBN:951-39-1785-1
dc.identifier.uri http://hdl.handle.net/123456789/13139
dc.description.abstract Canine parvovirus (CPV), a host range variant of feline panleukopenia virus (FPV), was first recognized in 1978 as a new virus infecting dogs.The CPV virion is formed from a single stranded DNA genome packed into a non-enveloped protein capsid. This capsid is composed of two structural proteins VP1 and VP2, formed by alternative splicing. The N-terminus of VP1 contains a potential nuclear localization signal (NLS) and phospholipase A2 (PLA2) like motif. In newly formed capsids the N-terminus of VP1 is enclosed within the capsid, but this sequence can be exposed by treatments with urea or heat without complete disintegration of the capsid. To initiate infection, CPV binds to transferrin receptors (TfRs) on the cell surface, and enters the cells by clathrin-mediated endocytosis. Productive infection is dependent on the acidic pH of endocytic vesicles as well as the integrity of microtubular the network. Although many details about CPV entry have been solved so far, the endocytic entry pathway, the course of events leading to penetration to the cytoplasm and the steps preceding nuclear import are still unknown. This thesis was designed to clarify the missing links of the CPV entry process using cell biological methods. The findings of this thesis suggest that after CPV enters the cells by clathrin-mediated endocytosis some receptor bound viruses are transported to recycling endosomes and some of those virus TfR complexes are redirected to the degradative pathway, ending up in lysosomes. Parvoviral phospholipase A2 (PLA2) activity located in the N-terminal part of viral capsid protein-1 (VP1) is triggered by treatments of acidic buffers or by heating. This amino acid sequence is exposed during the entry at 3-8 h post infection (p.i.)in lysosomal vesicles, indicating that the acidic lysosomal environment may trigger the activation of viral PLA2. This further suggests that viral PLA2 activity might be utilized in the membrane penetration process. Endosomal vesicles were not found to be disrupted by CPV infection, but the CPV was found to modify permeability of the endosomal/lysosomal membranes causing the release of the small (Mr 3000) dextran particles to the cytoplasm after 8 h of infection. After penetration into the cytosol, CPV capsids were transported towards the nucleus along microtubules in a dynein-dependent manner. en
dc.description.abstract Sanna Suikkasen väitöskirjatyössä havaittiin, että koiran parvovirus tarvitsee solun tarjoamaa kuljetuskoneistoa edetäkseen sen sisällä ja happamia olosuhteita pystyäkseen lisääntymään. Tulokset antavat kehykset viruksen ja sen läheisten sukulaisten solunsisäisen reitin tarkemmalle tutkimukselle ja luovat pohjaa viruslääkkeiden suunnitteluun. Mielenkiintoa parvoviruksien tutkimukseen lisää tutkijan mielestä myös kiinnostus parvopartikkeleiden geeniterapiasovellutuksiin. Koiran parvovirus eriytyi kissan panleukopeniaviruksesta 1970-luvun lopulla ja levisi nopeasti ympäri maailmaa. Se aiheuttaa aikuisille koirille ankaraa ripulia ja pennuille tappavia sydänlihastulehduksia. Parvovirukset aiheuttavat tauteja myös lukuisille muille eläimille kuten lehmille, sioille ja turkiseläimille, mistä seuraa myös rahallisia menetyksiä. Ihmisiä vaanii oma parvovirus B19 eli parvorokkovirus, joka aiheuttaa ihottumaa, niveloireita, sikiöpöhön tai sikiön kuoleman sekä hematologisia komplikaatioita. Parvovirusten ja muidenkin vaipattomien virusten solunsisäistä liikennettä tunnetaan edelleen huonosti. fi
dc.language.iso eng
dc.publisher University of Jyväskylä
dc.relation.ispartofseries Jyväskylä studies in biological and environmental science;1456-9701 ;122
dc.relation.isversionof ISBN 951-39-1508-5
dc.title Cell biology of canine parvovirus entry
dc.type Diss. fi
dc.identifier.urn URN:ISBN:951-39-1785-1
dc.subject.ysa virukset
dc.subject.ysa koira
dc.type.dcmitype Text en
dc.type.ontasot Väitöskirja fi
dc.type.ontasot Doctoral dissertation en
dc.contributor.tiedekunta Matemaattis-luonnontieteellinen tiedekunta fi
dc.contributor.tiedekunta Faculty of Mathematics and Science en
dc.contributor.yliopisto University of Jyväskylä en
dc.contributor.yliopisto Jyväskylän yliopisto fi

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