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dc.contributor.advisorRinaldo, Christine Hanssen
dc.contributor.authorSharma, Biswa Nath
dc.date.accessioned2014-11-28T14:38:35Z
dc.date.available2014-11-28T14:38:35Z
dc.date.issued2014-09-19
dc.description.abstractThe ubiquitous human BK and JC polyomaviruses cause the diseases polyomavirus-associated nephropathy, hemoragic cystitis and progressive multifocal leukoencephalopathy in immunosuppressed patients. There are no antiviral drugs for these diseases which often lead to kidney graft loss, severe disability and premature death. As a first step in the evaluation of the malaria drug artesunate as a future treatment option, we investigated the effect on BK- and JC polyomavirus replication in cell cultures. Our results show that artesunate inhibits BKPyV replication in kidney tubular epithelial cells and urothelial cells, the host cells for BK Polyomavirus in PyVAN and PyVHC. Similarly, artesunate inhibits JC polyomavirus replication in COS-7 cells. Slower cell division was also seen but this was transient. The exact mechanism for viral inhibition is not known yet but probably involves cellular proteins. Taken together, our results suggest that artesunate could be beneficial for treatment of polyomavirus diseases but first, carefully designed clinical studies are needed.en
dc.description.doctoraltypeph.d.en
dc.description.popularabstractPolyomavirus BK forårsaker nyreskade og blærebetennelse hos henholdsvis nyretransplanterte og beinmargstransplanterte pasienter, mens polyomavirus JC forårsaker en progressiv flekkvis ødeleggelse av hvit substans i hjernen hos ulike pasientgrupper med immunsvikt. Det finnes ingen antiviral behandling for disse sykdommene, som ofte fører til tap av transplantert nyre, funksjonshemming og død. Vi har undersøkt om det godt utprøvde malaria medikamentet artesunate har potensiale som fremtidig behandling. Våre resultater viser at artesunate hemmer nydanning av både polyomavirus BK og JC i cellekultur. Samtidig fører artesunate til at cellene vokser saktere, men denne effekten er kortvarig og forbigående. Den eksakte mekanismen for den antivirale effekten er ikke kjent, men involverer sannsynligvis cellulære proteiner. Vår konklusjon er at artesunate kan være nyttig for behandling av sykdom forårsaket av polyomavirus BK og JC, men at det først må gjennomføres nøye planlagte kliniske studier.en
dc.description.sponsorshipThe Northern Norway Regional Health Authority Medical Research Programen
dc.descriptionPapers number 2 and 3, and appendix I of this thesis are not available in Munin: <br>2. Li, R., Sharma, B.N., Linder, S., Gutteberg, T.J., Hirsch, H.H., Rinaldo, C.H.: 'Characteristics of polyomavirus BK (BKPyV) infection in primary human urothelial cells', Virology 440(2013), 41-50, available at <a href=http://dx.doi.org/10.1016/j.virol.2013.01.024>http://dx.doi.org/10.1016/j.virol.2013.01.024</a> <br>3. Biswa Nath Sharma, Manfred Marschall, and Christine Hanssen Rinaldo: 'Artesunate Inhibits Replication of BK Polyomavirus in Primary Human Urothelial Cells', manuscript. <br>Appendix I. Rinaldo, C.H., Tylden, G.D., Sharma, B.N.: 'The human polyomavirus BK (BKPyV): virological background and clinical implications', APMIS 121(2013), 728-745, available at <a href=http://dx.doi.org/10.1111/apm.12134>http://dx.doi.org/10.1111/apm.12134</a>en
dc.identifier.urihttps://hdl.handle.net/10037/6845
dc.identifier.urnURN:NBN:no-uit_munin_6444
dc.language.isoengen
dc.publisherUiT The Arctic University of Norwayen
dc.publisherUiT Norges arktiske universiteten
dc.rights.accessRightsopenAccess
dc.rights.holderCopyright 2014 The Author(s)
dc.subject.courseIDDOKTOR-003en
dc.subjectVDP::Medical disciplines: 700::Health sciences: 800::Other health science disciplines: 829en
dc.subjectVDP::Medisinske Fag: 700::Helsefag: 800::Andre helsefag: 829en
dc.titleInvestigation of the antiviral effects of artesunate on BK and JC polyomavirus replicationen
dc.typeDoctoral thesisen
dc.typeDoktorgradsavhandlingen


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