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[{"key": "dc.contributor.advisor", "value": "Marjom\u00e4ki, Varpu", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Laajala, Mira", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Myllym\u00e4ki, Laura", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2023-06-30T07:33:38Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2023-06-30T07:33:38Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2023", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/88146", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Enterovirukset ovat yleisi\u00e4 RNA-viruksia, jotka aiheuttavat monenlaisia sairauksia ihmisille. Huolimatta pyrkimyksist\u00e4 kehitt\u00e4\u00e4 tehokkaita ja laajakirjoisia antiviraaleja, t\u00e4ll\u00e4 hetkell\u00e4 enterovirusinfektioiden hoitamiseksi ei ole kliinisesti hyv\u00e4ksyttyj\u00e4 l\u00e4\u00e4kkeit\u00e4, ja uusia antiviraalistrategioita tarvitaan. Monet virukset vuorovaikuttavat is\u00e4nt\u00e4solun ubiquitomi-j\u00e4rjestelm\u00e4n kanssa. Soluissa t\u00e4m\u00e4 j\u00e4rjestelm\u00e4 osallistuu useisiin perustavanlaatuisiin prosesseihin sek\u00e4 substraattien proteosomaaliseen hajotukseen. Koska ubiquitomi-j\u00e4rjestelm\u00e4 voi sek\u00e4 est\u00e4\u00e4, ett\u00e4 edist\u00e4\u00e4 virusinfektioita erilaisten entsyymien v\u00e4lityksell\u00e4, t\u00e4m\u00e4n tutkielman tarkoituksena oli selvent\u00e4\u00e4 sen merkityst\u00e4 enteroviruksille. Aiemmin yhdeks\u00e4n ubiquitomigeenin havaittiin vaikuttavan enteroviruksiin kuuluvan coxsackievirus B3:n (CVB3) infektioon. Havaintojen vahvistamiseksi t\u00e4ss\u00e4 tutkielmassa kyseiset geenit hiljennettiin pienill\u00e4 h\u00e4iritsevill\u00e4 RNA-molekyyleill\u00e4 (siRNA), ja transfektoiduissa soluissa etenev\u00e4\u00e4 CVB3-infektiota seurattiin immunofluoresenssileimauksella ja konfokaalimikroskopialla, sek\u00e4 western blot -menetelm\u00e4ll\u00e4. CVB3-infektion lis\u00e4ksi my\u00f6s coxsackievirus B1:n (CVB1) ja echovirus 30:n (EV30) infektioita tarkasteltiin mahdollisten laaja-alaisten vaikutusten selvitt\u00e4miseksi. Yhdeks\u00e4st\u00e4 geenist\u00e4 kolmen havaittiin vaikuttavan kaikkiin tutkittuihin viruksiin. N\u00e4iden geenien, UCHL1, CHD4 ja FBXL14, hiljent\u00e4misell\u00e4 oli infektioita alentava vaikutus. CVB1- ja EV30-infektiot alenivat my\u00f6s, kun CAND2-geeni hiljennettiin. Tulosten perusteella valituille siRNA-molekyyleille tehtiin sytotoksisuuskoe, jotta saataisiin lis\u00e4tietoa merkitt\u00e4v\u00e4ksi havaittujen ubiquitomitekij\u00f6iden potentiaalista antiviraalikehityksess\u00e4. Vaikka UCHL1-, CHD4- ja FBXL14-geenien hiljent\u00e4misell\u00e4 oli pieni vaikutus solujen elinkykyyn, mik\u00e4\u00e4n siRNA-k\u00e4sittelyist\u00e4 ei ollut \u00e4\u00e4rimm\u00e4isen toksinen. Havaitut ubiquitomitekij\u00f6iden vaikutukset voivat liitty\u00e4 niiden rooliin enterovirusten elinsykliss\u00e4, tai prosesseihin kuten immuunipuolustus ja solusyklin s\u00e4\u00e4tely. Vaikka tarkkoja antiviraalimekanismeja ei viel\u00e4 tunneta, l\u00f6yd\u00f6s useille enteroviruksille yhteisist\u00e4 ubiquitomitekij\u00f6ist\u00e4 on lupaava.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Enteroviruses are ubiquitous RNA viruses, capable of causing a wide spectrum of diseases in humans. Despite the efforts to develop effective broad-spectrum antivirals, currently there are no clinically approved therapeutics against enteroviral infections, and thus, novel antiviral strategies are needed. Many viruses can interact with the cellular ubiquitome system, which mediates numerous cellular processes and proteasomal degradation of protein substrates. This system can both hinder and promote viral infections, mainly through the activities of ubiquitin ligases and deubiquitinating enzymes. The aim of this thesis was to examine the importance of ubiquitome in enteroviral infections. Previously, nine ubiquitome-related genes were connected to coxsackievirus B3 (CVB3), a type of enterovirus. To validate the previous findings, in this study, the expression of the genes was knocked down with small interfering RNAs (siRNA) and the progression of CVB3 infection was monitored using immunofluorescence labelling and confocal microscopy, as well as western blotting. In addition to CVB3, infections of coxsackievirus B1 (CVB1) and echovirus 30 (EV30) were examined to assess the broad-spectrum effects of silencing ubiquitome-related factors. Knockdown of three genes, namely UCHL1, CHD4 and FBXL14, reduced infections caused by all enteroviruses tested. In addition, the knockdown of CAND2 inhibited CVB1 and EV30 infections. To further inspect the potential of these ubiquitome-related factors in antiviral development, a cytotoxicity assay was conducted for the hit siRNAs. Although UCHL1, FBXL14 and CHD4 knockdown had a slight effect on cell viability, none of the hit siRNA treatments were radically toxic. The anti-enteroviral effects observed in this study may be related to processes such as immune responses or cell cycle regulation. On the other hand, the viruses may also require ubiquitome factors to complete different stages of their life cycle. The exact antiviral mechanisms, however, remain to be determined. In terms of developing broad-spectrum antivirals, the finding that several enteroviral serotypes can utilize same ubiquitome factors is promising.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Miia Hakanen (mihakane@jyu.fi) on 2023-06-30T07:33:38Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2023-06-30T07:33:38Z (GMT). No. of bitstreams: 0\n Previous issue date: 2023", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "47", "language": "", "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.language.iso", "value": "eng", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": null, "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "antivirals", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "ubiquitination", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "ubiquitin-proteasome system", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "The importance of ubiquitome in enteroviral infections", "language": "", "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-202306304292", "language": "", "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.copyright", "value": "\u00a9 The Author(s)", "language": null, "element": "rights", "qualifier": "copyright", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "openAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "enterovirukset", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "infektiot", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "proteiinit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "virustaudit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "geenit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "enteroviruses", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "infections", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "proteins", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "virus diseases", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "genes", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}]
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