Mechanisms of coxsackievirus B5 mediated β-cell death depend on the multiplicity of infection
Coxsackievirus infections may trigger and accelerate pancreatic β‐cell death, leading to type I diabetes. Unrestricted coxsackievirus B5 replication in cultured β‐cells inoculated with high multiplicity leads to rapid lytic cell death. Evidence from other virus‐host cell systems indicates that host...
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| Veröffentlicht in: | Journal of medical virology 2004-04, Vol.72 (4), p.586-596 |
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| creator | Rasilainen, Suvi Ylipaasto, Petri Roivainen, Merja Lapatto, Risto Hovi, Tapani Otonkoski, Timo |
| description | Coxsackievirus infections may trigger and accelerate pancreatic β‐cell death, leading to type I diabetes. Unrestricted coxsackievirus B5 replication in cultured β‐cells inoculated with high multiplicity leads to rapid lytic cell death. Evidence from other virus‐host cell systems indicates that host cell responses to infection may depend on the multiplicity of infection (MOI). Thus, the aim of this study was to compare the mechanisms of β‐cell death during high versus low multiplicity of coxsackievirus B5 infection. Cultures of highly differentiated mouse insulinoma cells and primary adult human islets were infected with coxsackievirus B5 at multiplicities of >1,000 or |
| doi_str_mv | 10.1002/jmv.20043 |
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Unrestricted coxsackievirus B5 replication in cultured β‐cells inoculated with high multiplicity leads to rapid lytic cell death. Evidence from other virus‐host cell systems indicates that host cell responses to infection may depend on the multiplicity of infection (MOI). Thus, the aim of this study was to compare the mechanisms of β‐cell death during high versus low multiplicity of coxsackievirus B5 infection. Cultures of highly differentiated mouse insulinoma cells and primary adult human islets were infected with coxsackievirus B5 at multiplicities of >1,000 or <0.5 TCID50 per cell. The results of nuclear morphology and viability stainings, TUNEL staining and electrophoretic DNA fragmentation analysis showed high multiplicity infection to predominantly induce necrosis and transient apoptosis. In low multiplicity culture, however, necrosis was only moderately induced and apoptosis increased steadily with time. This was best demonstrated by a tenfold higher apoptosis/necrosis ratio than after high multiplicity inoculation. Expression of γ‐glutamyl cysteine synthetase increased in both infective cultures but the level of intracellular glutathione permanently depleted only at high multiplicity and recovered fully at low multiplicity. Thus, apoptosis represents an important mechanism of β‐cell death after low multiplicity of coxsackievirus B5 infection. This process is associated with maintenance of a physiological intracellular glutathione profile differing dramatically from the high multiplicity infection during which necrosis dominates and intracellular thiol balance deteriorates. These data suggest that the pattern and mechanisms of coxsackievirus B5 infection induced β‐cell death depend on the MOI. J. Med. Virol. 72:586–596, 2004. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 0146-6615</identifier><identifier>EISSN: 1096-9071</identifier><identifier>DOI: 10.1002/jmv.20043</identifier><identifier>PMID: 14981761</identifier><identifier>CODEN: JMVIDB</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Apoptosis ; Benzimidazoles - metabolism ; Biological and medical sciences ; Cell Death ; Cell Line, Tumor ; Cell Nucleus - ultrastructure ; Cells, Cultured ; coxsackievirus B5 ; diabetes ; DNA Fragmentation ; enterovirus ; Enterovirus B, Human - pathogenicity ; Ethidium - analogs & derivatives ; Ethidium - metabolism ; Fundamental and applied biological sciences. Psychology ; g-glutamyl cysteine synthase ; Glutamate-Cysteine Ligase - biosynthesis ; glutathione ; Glutathione - analysis ; Human viral diseases ; Humans ; In Situ Nick-End Labeling ; Infectious diseases ; Insulinoma ; islet ; Islets of Langerhans - pathology ; Islets of Langerhans - virology ; Medical sciences ; Mice ; Microbiology ; Miscellaneous ; Necrosis ; Nitrites - analysis ; pathogenesis ; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains ; Viral diseases ; Virology</subject><ispartof>Journal of medical virology, 2004-04, Vol.72 (4), p.586-596</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><rights>2004 INIST-CNRS</rights><rights>Copyright 2004 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4203-c9d9ffd31a861ed0bb98865bdded12fe5b27a33cd889d198f436fa7787ad72fd3</citedby><cites>FETCH-LOGICAL-c4203-c9d9ffd31a861ed0bb98865bdded12fe5b27a33cd889d198f436fa7787ad72fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjmv.20043$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjmv.20043$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15522012$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14981761$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rasilainen, Suvi</creatorcontrib><creatorcontrib>Ylipaasto, Petri</creatorcontrib><creatorcontrib>Roivainen, Merja</creatorcontrib><creatorcontrib>Lapatto, Risto</creatorcontrib><creatorcontrib>Hovi, Tapani</creatorcontrib><creatorcontrib>Otonkoski, Timo</creatorcontrib><title>Mechanisms of coxsackievirus B5 mediated β-cell death depend on the multiplicity of infection</title><title>Journal of medical virology</title><addtitle>J. Med. Virol</addtitle><description>Coxsackievirus infections may trigger and accelerate pancreatic β‐cell death, leading to type I diabetes. Unrestricted coxsackievirus B5 replication in cultured β‐cells inoculated with high multiplicity leads to rapid lytic cell death. Evidence from other virus‐host cell systems indicates that host cell responses to infection may depend on the multiplicity of infection (MOI). Thus, the aim of this study was to compare the mechanisms of β‐cell death during high versus low multiplicity of coxsackievirus B5 infection. Cultures of highly differentiated mouse insulinoma cells and primary adult human islets were infected with coxsackievirus B5 at multiplicities of >1,000 or <0.5 TCID50 per cell. The results of nuclear morphology and viability stainings, TUNEL staining and electrophoretic DNA fragmentation analysis showed high multiplicity infection to predominantly induce necrosis and transient apoptosis. In low multiplicity culture, however, necrosis was only moderately induced and apoptosis increased steadily with time. This was best demonstrated by a tenfold higher apoptosis/necrosis ratio than after high multiplicity inoculation. Expression of γ‐glutamyl cysteine synthetase increased in both infective cultures but the level of intracellular glutathione permanently depleted only at high multiplicity and recovered fully at low multiplicity. Thus, apoptosis represents an important mechanism of β‐cell death after low multiplicity of coxsackievirus B5 infection. This process is associated with maintenance of a physiological intracellular glutathione profile differing dramatically from the high multiplicity infection during which necrosis dominates and intracellular thiol balance deteriorates. These data suggest that the pattern and mechanisms of coxsackievirus B5 infection induced β‐cell death depend on the MOI. J. Med. Virol. 72:586–596, 2004. © 2004 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Benzimidazoles - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell Death</subject><subject>Cell Line, Tumor</subject><subject>Cell Nucleus - ultrastructure</subject><subject>Cells, Cultured</subject><subject>coxsackievirus B5</subject><subject>diabetes</subject><subject>DNA Fragmentation</subject><subject>enterovirus</subject><subject>Enterovirus B, Human - pathogenicity</subject><subject>Ethidium - analogs & derivatives</subject><subject>Ethidium - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>g-glutamyl cysteine synthase</subject><subject>Glutamate-Cysteine Ligase - biosynthesis</subject><subject>glutathione</subject><subject>Glutathione - analysis</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>In Situ Nick-End Labeling</subject><subject>Infectious diseases</subject><subject>Insulinoma</subject><subject>islet</subject><subject>Islets of Langerhans - pathology</subject><subject>Islets of Langerhans - virology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Necrosis</subject><subject>Nitrites - analysis</subject><subject>pathogenesis</subject><subject>Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains</subject><subject>Viral diseases</subject><subject>Virology</subject><issn>0146-6615</issn><issn>1096-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtuFDEQRS1ERIbAgh9AvSFSFp247G4_liQiA1ECEoKAWGC57bLGST-GdnfI_BYfwjelJzOQFWJTtTn3VukQ8gLoIVDKjq6am0NGacEfkRlQLXJNJTwmMwqFyIWAcpc8TemKUqo0Y0_ILhRagRQwI98v0C1sG1OTsi5krrtN1l1HvIn9mLLjMmvQRzugz37_yh3WdebRDotpLrH1WddmwwKzZqyHuKyji8NqXRPbgG6IXfuM7ARbJ3y-3Xvk8-mbTydv8_MP83cnr89zVzDKc6e9DsFzsEoAelpVWilRVt6jBxawrJi0nDuvlPagVSi4CFZKJa2XbArukf1N77LvfoyYBtPEtH7XttiNySgKSohC_hcEzUrBgE7gwQZ0fZdSj8Es-9jYfmWAmrV1M1k399Yn9uW2dKwmXw_kVvMEvNoCNjlbh962LqYHriwZo8Am7mjD_Yw1rv590ZxdXP45nW8SMQ14-zdh-2sjJJel-fJ-bjS__Pjt-Ksyc34H28Wpbw</recordid><startdate>200404</startdate><enddate>200404</enddate><creator>Rasilainen, Suvi</creator><creator>Ylipaasto, Petri</creator><creator>Roivainen, Merja</creator><creator>Lapatto, Risto</creator><creator>Hovi, Tapani</creator><creator>Otonkoski, Timo</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Liss</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200404</creationdate><title>Mechanisms of coxsackievirus B5 mediated β-cell death depend on the multiplicity of infection</title><author>Rasilainen, Suvi ; Ylipaasto, Petri ; Roivainen, Merja ; Lapatto, Risto ; Hovi, Tapani ; Otonkoski, Timo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4203-c9d9ffd31a861ed0bb98865bdded12fe5b27a33cd889d198f436fa7787ad72fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Benzimidazoles - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell Death</topic><topic>Cell Line, Tumor</topic><topic>Cell Nucleus - ultrastructure</topic><topic>Cells, Cultured</topic><topic>coxsackievirus B5</topic><topic>diabetes</topic><topic>DNA Fragmentation</topic><topic>enterovirus</topic><topic>Enterovirus B, Human - pathogenicity</topic><topic>Ethidium - analogs & derivatives</topic><topic>Ethidium - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>g-glutamyl cysteine synthase</topic><topic>Glutamate-Cysteine Ligase - biosynthesis</topic><topic>glutathione</topic><topic>Glutathione - analysis</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>In Situ Nick-End Labeling</topic><topic>Infectious diseases</topic><topic>Insulinoma</topic><topic>islet</topic><topic>Islets of Langerhans - pathology</topic><topic>Islets of Langerhans - virology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Necrosis</topic><topic>Nitrites - analysis</topic><topic>pathogenesis</topic><topic>Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains</topic><topic>Viral diseases</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rasilainen, Suvi</creatorcontrib><creatorcontrib>Ylipaasto, Petri</creatorcontrib><creatorcontrib>Roivainen, Merja</creatorcontrib><creatorcontrib>Lapatto, Risto</creatorcontrib><creatorcontrib>Hovi, Tapani</creatorcontrib><creatorcontrib>Otonkoski, Timo</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medical virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rasilainen, Suvi</au><au>Ylipaasto, Petri</au><au>Roivainen, Merja</au><au>Lapatto, Risto</au><au>Hovi, Tapani</au><au>Otonkoski, Timo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanisms of coxsackievirus B5 mediated β-cell death depend on the multiplicity of infection</atitle><jtitle>Journal of medical virology</jtitle><addtitle>J. Med. Virol</addtitle><date>2004-04</date><risdate>2004</risdate><volume>72</volume><issue>4</issue><spage>586</spage><epage>596</epage><pages>586-596</pages><issn>0146-6615</issn><eissn>1096-9071</eissn><coden>JMVIDB</coden><abstract>Coxsackievirus infections may trigger and accelerate pancreatic β‐cell death, leading to type I diabetes. Unrestricted coxsackievirus B5 replication in cultured β‐cells inoculated with high multiplicity leads to rapid lytic cell death. Evidence from other virus‐host cell systems indicates that host cell responses to infection may depend on the multiplicity of infection (MOI). Thus, the aim of this study was to compare the mechanisms of β‐cell death during high versus low multiplicity of coxsackievirus B5 infection. Cultures of highly differentiated mouse insulinoma cells and primary adult human islets were infected with coxsackievirus B5 at multiplicities of >1,000 or <0.5 TCID50 per cell. The results of nuclear morphology and viability stainings, TUNEL staining and electrophoretic DNA fragmentation analysis showed high multiplicity infection to predominantly induce necrosis and transient apoptosis. In low multiplicity culture, however, necrosis was only moderately induced and apoptosis increased steadily with time. This was best demonstrated by a tenfold higher apoptosis/necrosis ratio than after high multiplicity inoculation. Expression of γ‐glutamyl cysteine synthetase increased in both infective cultures but the level of intracellular glutathione permanently depleted only at high multiplicity and recovered fully at low multiplicity. Thus, apoptosis represents an important mechanism of β‐cell death after low multiplicity of coxsackievirus B5 infection. This process is associated with maintenance of a physiological intracellular glutathione profile differing dramatically from the high multiplicity infection during which necrosis dominates and intracellular thiol balance deteriorates. These data suggest that the pattern and mechanisms of coxsackievirus B5 infection induced β‐cell death depend on the MOI. J. Med. Virol. 72:586–596, 2004. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>14981761</pmid><doi>10.1002/jmv.20043</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals Apoptosis Benzimidazoles - metabolism Biological and medical sciences Cell Death Cell Line, Tumor Cell Nucleus - ultrastructure Cells, Cultured coxsackievirus B5 diabetes DNA Fragmentation enterovirus Enterovirus B, Human - pathogenicity Ethidium - analogs & derivatives Ethidium - metabolism Fundamental and applied biological sciences. Psychology g-glutamyl cysteine synthase Glutamate-Cysteine Ligase - biosynthesis glutathione Glutathione - analysis Human viral diseases Humans In Situ Nick-End Labeling Infectious diseases Insulinoma islet Islets of Langerhans - pathology Islets of Langerhans - virology Medical sciences Mice Microbiology Miscellaneous Necrosis Nitrites - analysis pathogenesis Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains Viral diseases Virology |
| title | Mechanisms of coxsackievirus B5 mediated β-cell death depend on the multiplicity of infection |
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