The role of calpains in enterovirus infection

Enterovirukset ovat viruspeitteettömien, positiivisten RNA-virusten ryhmään kuuluva virusperhe, jonka jäsenet aiheuttamat mitä monituisimpia tauteja suu- ja sorkkataudista aina aivokalvontulehdukseen. Aikaisemmat tutkimustulokset ovat osoittaneet, että calpainien toiminnan hiljentäminen...

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Päätekijä: Kangasniemi, Niko
Muut tekijät: Matemaattis-luonnontieteellinen tiedekunta, Faculty of Sciences, Bio- ja ympäristötieteiden laitos, Department of Biological and Environmental Science, Jyväskylän yliopisto, University of Jyväskylä
Aineistotyyppi: Pro gradu
Kieli:eng
Julkaistu: 2019
Aiheet:
Linkit: https://jyx.jyu.fi/handle/123456789/68784
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author Kangasniemi, Niko
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_facet Kangasniemi, Niko Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä Kangasniemi, Niko Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_sort Kangasniemi, Niko
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description Enterovirukset ovat viruspeitteettömien, positiivisten RNA-virusten ryhmään kuuluva virusperhe, jonka jäsenet aiheuttamat mitä monituisimpia tauteja suu- ja sorkkataudista aina aivokalvontulehdukseen. Aikaisemmat tutkimustulokset ovat osoittaneet, että calpainien toiminnan hiljentäminen solussa estää enterovirusinfektion etenemisen ja uuden virus-RNA:n tuottamisen. Enterovirukset tuottavat proteiininsa yhteenliittyneenä polyproteiinissa, jonka viruksen proteaasit pilkkovat rakenteellisiksi ja toiminnallisiksi proteiineiksi. Tämän Pro Gradu –tutkielman tavoitteena oli selvittää millainen rooli calpaineilla on Echovirus 1 ja Coxsackievirus B3 –infektioissa. Erilaisten kokeiden avulla selvitettiin, missä vaiheessa infektiota calpainit ovat sille tärkeitä ja millä tavalla. Calpainien toiminnan estäminen ennen 120 minuutin aikapistettä esti sekä Echovirus 1, että Coxsackievirus B3 –infektion. Myös enterovirusinfektioille tyypilliset kalvomuutokset solussa estyivät, kun calpainien toiminta estettiin. Pilkkomakokeessa selvisi, että calpainit kykenevät pilkkomaan Coxsackievirus B1:n polyproteiinia. Kokonaisuudessaan nämä tulokset viittaavat siihen, että calpainien toiminta enterovirusten infektiossa tapahtuu viruksen sisäänmenon jälkeen, mutta ennen kalvojen uudelleenjärjestelyä ja RNA:n replikaatiota; calpainit mitä todennäköisimmin osallistuvat polyproteiinin pilkkomiseen. Enteroviruses are a group of non-enveloped positive-sense RNA viruses that cause a variety of diseases ranging from foot-and-mouth disease to meningitis. Previous studies have shown that the inhibition of calpains prevents the enterovirus infection after entry and RNA release into the cytoplasm. Upon protein translation enteroviruses produce a 250 kDa polyprotein that is cleaved into structural and non-structural viral proteins. These cleavages are performed by viral proteases. However, previous studies have shown that the inhibition of the cellular calpains inhibits the enterovirus RNA-replication. Aim of this study is to investigate the role of calpains in Echovirus 1 and Coxsackievirus B3 infections. An array of experiments was performed in order to determine the time window when calpains are required for the infection and to assess the possible mechanism they might have. The inhibition of calpains before 120 min post-infection inhibited both Echovirus 1 and Coxsackievirus B3 infection. The inhibition of calpains prevented the intracellular membrane modifications characteristic to enterovirus infection. In a cleavage experiment calpains were found capable of processing the Coxsackievirus B1 polyprotein. These results suggest that the role of calpains in the enterovirus infection is after entry but before membrane rearrangements and RNA replication, most likely in the polyprotein processing.
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spellingShingle Kangasniemi, Niko The role of calpains in enterovirus infection calpain CVB3 EV1 infection timetable picornavirus polyprotein Solu- ja molekyylibiologia Cell and molecular biology 4013 virukset infektiot enterovirukset viruses infections enteroviruses
title The role of calpains in enterovirus infection
title_full The role of calpains in enterovirus infection
title_fullStr The role of calpains in enterovirus infection The role of calpains in enterovirus infection
title_full_unstemmed The role of calpains in enterovirus infection The role of calpains in enterovirus infection
title_short The role of calpains in enterovirus infection
title_sort role of calpains in enterovirus infection
title_txtP The role of calpains in enterovirus infection
topic calpain CVB3 EV1 infection timetable picornavirus polyprotein Solu- ja molekyylibiologia Cell and molecular biology 4013 virukset infektiot enterovirukset viruses infections enteroviruses
topic_facet 4013 CVB3 Cell and molecular biology EV1 Solu- ja molekyylibiologia calpain enterovirukset enteroviruses infection timetable infections infektiot picornavirus polyprotein virukset viruses
url https://jyx.jyu.fi/handle/123456789/68784 http://www.urn.fi/URN:NBN:fi:jyu-202004302991
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