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Pathogenesis of Virus-Induced Diabetes in Mice
Male CD-l mice were challenged with a diabetogenic strain (E2) of coxsackievirus B4 (CVB4). At 7 weeks, 6 months, and 1 year after inoculation, mean histopathologic scores, postprandial blood glucose levels, and serum levels of antibody to islet cells were significantly elevated and mean fasting ser...
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Published in: | The Journal of infectious diseases 1995-05, Vol.171 (5), p.1131-1138 |
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description | Male CD-l mice were challenged with a diabetogenic strain (E2) of coxsackievirus B4 (CVB4). At 7 weeks, 6 months, and 1 year after inoculation, mean histopathologic scores, postprandial blood glucose levels, and serum levels of antibody to islet cells were significantly elevated and mean fasting serum insulin levels significantly reduced in infected mice versus uninfected controls (P < .001 for each). At 7 weeks after infection, viral RNA, but not protein or infectious virus, was demonstrated in the pancreases of most infected mice. The pancreases of 4 of 12 and 0 of 10 infected animals were positive for viral RNA at 6 months and at 1 year after infection, respectively. Interferon-γ-stimulated peritoneal macrophages were cytotoxic to islet cells with and without sera with high titers of islet cell autoantibody (ICA). Thus, islet cell destruction in mice infected with CVB4 strain E2 is associated with chronic islet cell inflammation, elevation of islet cell antibody, and prolonged presence of viral RNA in the pancreas. Stimulated peritoneal macrophages lyse islet cells directly and by an antibody-dependent mechanism. |
doi_str_mv | 10.1093/infdis/171.5.1131 |
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At 7 weeks, 6 months, and 1 year after inoculation, mean histopathologic scores, postprandial blood glucose levels, and serum levels of antibody to islet cells were significantly elevated and mean fasting serum insulin levels significantly reduced in infected mice versus uninfected controls (P < .001 for each). At 7 weeks after infection, viral RNA, but not protein or infectious virus, was demonstrated in the pancreases of most infected mice. The pancreases of 4 of 12 and 0 of 10 infected animals were positive for viral RNA at 6 months and at 1 year after infection, respectively. Interferon-γ-stimulated peritoneal macrophages were cytotoxic to islet cells with and without sera with high titers of islet cell autoantibody (ICA). Thus, islet cell destruction in mice infected with CVB4 strain E2 is associated with chronic islet cell inflammation, elevation of islet cell antibody, and prolonged presence of viral RNA in the pancreas. Stimulated peritoneal macrophages lyse islet cells directly and by an antibody-dependent mechanism.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/171.5.1131</identifier><identifier>PMID: 7751687</identifier><identifier>CODEN: JIDIAQ</identifier><language>eng</language><publisher>Chicago, IL: The University of Chicago Press</publisher><subject>Animals ; Autoantibodies - blood ; Base Sequence ; Biological and medical sciences ; Blood Glucose - analysis ; Coxsackievirus Infections - immunology ; Coxsackievirus Infections - pathology ; Coxsackievirus Infections - virology ; Cytotoxicity Tests, Immunologic ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus - immunology ; Diabetes Mellitus - pathology ; Diabetes Mellitus - virology ; Enterovirus B, Human - pathogenicity ; Experimental viral diseases and models ; Infections ; Infectious diseases ; Insulin ; Insulin - blood ; Islet cells ; Islets of Langerhans - immunology ; Islets of Langerhans - pathology ; Islets of Langerhans - virology ; Macrophages ; Major Articles ; Male ; Medical sciences ; Mice ; Molecular Sequence Data ; Organ Specificity ; Pancreas ; Pancreas - chemistry ; Pancreas - pathology ; Pancreas - virology ; RNA, Viral - analysis ; Type 1 diabetes mellitus ; Viral diseases ; Viral RNA ; Viruses</subject><ispartof>The Journal of infectious diseases, 1995-05, Vol.171 (5), p.1131-1138</ispartof><rights>Copyright 1995 The University of Chicago</rights><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-e5d047d848ac888cf8f6d78814a616aca19e0073159b8455c437248f944d0cd43</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/30134538$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/30134538$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,58238,58471</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3498063$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7751687$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>See, Darryl M.</creatorcontrib><creatorcontrib>Tilles, Jeremiah G.</creatorcontrib><title>Pathogenesis of Virus-Induced Diabetes in Mice</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Male CD-l mice were challenged with a diabetogenic strain (E2) of coxsackievirus B4 (CVB4). At 7 weeks, 6 months, and 1 year after inoculation, mean histopathologic scores, postprandial blood glucose levels, and serum levels of antibody to islet cells were significantly elevated and mean fasting serum insulin levels significantly reduced in infected mice versus uninfected controls (P < .001 for each). At 7 weeks after infection, viral RNA, but not protein or infectious virus, was demonstrated in the pancreases of most infected mice. The pancreases of 4 of 12 and 0 of 10 infected animals were positive for viral RNA at 6 months and at 1 year after infection, respectively. Interferon-γ-stimulated peritoneal macrophages were cytotoxic to islet cells with and without sera with high titers of islet cell autoantibody (ICA). Thus, islet cell destruction in mice infected with CVB4 strain E2 is associated with chronic islet cell inflammation, elevation of islet cell antibody, and prolonged presence of viral RNA in the pancreas. Stimulated peritoneal macrophages lyse islet cells directly and by an antibody-dependent mechanism.</description><subject>Animals</subject><subject>Autoantibodies - blood</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - analysis</subject><subject>Coxsackievirus Infections - immunology</subject><subject>Coxsackievirus Infections - pathology</subject><subject>Coxsackievirus Infections - virology</subject><subject>Cytotoxicity Tests, Immunologic</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus - immunology</subject><subject>Diabetes Mellitus - pathology</subject><subject>Diabetes Mellitus - virology</subject><subject>Enterovirus B, Human - pathogenicity</subject><subject>Experimental viral diseases and models</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Insulin</subject><subject>Insulin - blood</subject><subject>Islet cells</subject><subject>Islets of Langerhans - immunology</subject><subject>Islets of Langerhans - pathology</subject><subject>Islets of Langerhans - virology</subject><subject>Macrophages</subject><subject>Major Articles</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Organ Specificity</subject><subject>Pancreas</subject><subject>Pancreas - chemistry</subject><subject>Pancreas - pathology</subject><subject>Pancreas - virology</subject><subject>RNA, Viral - analysis</subject><subject>Type 1 diabetes mellitus</subject><subject>Viral diseases</subject><subject>Viral RNA</subject><subject>Viruses</subject><issn>0022-1899</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><recordid>eNpFkEtPAjEUhRujQUR_gAuTWRh3A730OUuDD0gwSkBj3DSl7WgRZrCdSfTfOwTE1V1855zcfAidA-4CzkjPF7n1sQcCuqwLQOAAtYERkXIO5BC1Me73U5BZdoxOYlxgjCnhooVaQjDgUrRR90lXH-W7K1z0MSnz5MWHOqajwtbG2eTG67mrXEx8kTx4407RUa6X0Z3tbgc9393OBsN0_Hg_GlyPU0OBV6ljFlNhJZXaSClNLnNuhZRANQeujYbMYSwIsGwuKWOGEtGnMs8otdhYSjroaru7DuVX7WKlVj4at1zqwpV1VMAzDEBlE4Rt0IQyxuBytQ5-pcOPAqw2jtTWkWocKaY2jprOxW68nq-c3Td2Uhp-ueM6Gr3Mgy5Ms_AXIzSTmJP_mUWsyvCPMRDKyOa1dMt9rNz3nuvwqbgggqnh65uaTmZyQqagBuQXK02GzQ</recordid><startdate>19950501</startdate><enddate>19950501</enddate><creator>See, Darryl M.</creator><creator>Tilles, Jeremiah G.</creator><general>The University of Chicago Press</general><general>University of Chicago Press</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></search><sort><creationdate>19950501</creationdate><title>Pathogenesis of Virus-Induced Diabetes in Mice</title><author>See, Darryl M. ; Tilles, Jeremiah G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-e5d047d848ac888cf8f6d78814a616aca19e0073159b8455c437248f944d0cd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Animals</topic><topic>Autoantibodies - blood</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - analysis</topic><topic>Coxsackievirus Infections - immunology</topic><topic>Coxsackievirus Infections - pathology</topic><topic>Coxsackievirus Infections - virology</topic><topic>Cytotoxicity Tests, Immunologic</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus - immunology</topic><topic>Diabetes Mellitus - pathology</topic><topic>Diabetes Mellitus - virology</topic><topic>Enterovirus B, Human - pathogenicity</topic><topic>Experimental viral diseases and models</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Insulin</topic><topic>Insulin - blood</topic><topic>Islet cells</topic><topic>Islets of Langerhans - immunology</topic><topic>Islets of Langerhans - pathology</topic><topic>Islets of Langerhans - virology</topic><topic>Macrophages</topic><topic>Major Articles</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>Organ Specificity</topic><topic>Pancreas</topic><topic>Pancreas - chemistry</topic><topic>Pancreas - pathology</topic><topic>Pancreas - virology</topic><topic>RNA, Viral - analysis</topic><topic>Type 1 diabetes mellitus</topic><topic>Viral diseases</topic><topic>Viral RNA</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>See, Darryl M.</creatorcontrib><creatorcontrib>Tilles, Jeremiah G.</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><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>See, Darryl M.</au><au>Tilles, Jeremiah G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pathogenesis of Virus-Induced Diabetes in Mice</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>1995-05-01</date><risdate>1995</risdate><volume>171</volume><issue>5</issue><spage>1131</spage><epage>1138</epage><pages>1131-1138</pages><issn>0022-1899</issn><eissn>1537-6613</eissn><coden>JIDIAQ</coden><abstract>Male CD-l mice were challenged with a diabetogenic strain (E2) of coxsackievirus B4 (CVB4). At 7 weeks, 6 months, and 1 year after inoculation, mean histopathologic scores, postprandial blood glucose levels, and serum levels of antibody to islet cells were significantly elevated and mean fasting serum insulin levels significantly reduced in infected mice versus uninfected controls (P < .001 for each). At 7 weeks after infection, viral RNA, but not protein or infectious virus, was demonstrated in the pancreases of most infected mice. The pancreases of 4 of 12 and 0 of 10 infected animals were positive for viral RNA at 6 months and at 1 year after infection, respectively. Interferon-γ-stimulated peritoneal macrophages were cytotoxic to islet cells with and without sera with high titers of islet cell autoantibody (ICA). Thus, islet cell destruction in mice infected with CVB4 strain E2 is associated with chronic islet cell inflammation, elevation of islet cell antibody, and prolonged presence of viral RNA in the pancreas. Stimulated peritoneal macrophages lyse islet cells directly and by an antibody-dependent mechanism.</abstract><cop>Chicago, IL</cop><pub>The University of Chicago Press</pub><pmid>7751687</pmid><doi>10.1093/infdis/171.5.1131</doi><tpages>8</tpages></addata></record> |
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subjects | Animals Autoantibodies - blood Base Sequence Biological and medical sciences Blood Glucose - analysis Coxsackievirus Infections - immunology Coxsackievirus Infections - pathology Coxsackievirus Infections - virology Cytotoxicity Tests, Immunologic Diabetes Diabetes mellitus Diabetes Mellitus - immunology Diabetes Mellitus - pathology Diabetes Mellitus - virology Enterovirus B, Human - pathogenicity Experimental viral diseases and models Infections Infectious diseases Insulin Insulin - blood Islet cells Islets of Langerhans - immunology Islets of Langerhans - pathology Islets of Langerhans - virology Macrophages Major Articles Male Medical sciences Mice Molecular Sequence Data Organ Specificity Pancreas Pancreas - chemistry Pancreas - pathology Pancreas - virology RNA, Viral - analysis Type 1 diabetes mellitus Viral diseases Viral RNA Viruses |
title | Pathogenesis of Virus-Induced Diabetes in Mice |
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