Virus-Induced Abl and Fyn Kinase Signals Permit Coxsackievirus Entry through Epithelial Tight Junctions
Group B coxsackieviruses (CVBs) must cross the epithelium as they initiate infection, but the mechanism by which this occurs remains uncertain. The coxsackievirus and adenovirus receptor (CAR) is a component of the tight junction and is inaccessible to virus approaching from the apical surface. Many...
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Veröffentlicht in: | Cell 2006-01, Vol.124 (1), p.119-131 |
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description | Group B coxsackieviruses (CVBs) must cross the epithelium as they initiate infection, but the mechanism by which this occurs remains uncertain. The coxsackievirus and adenovirus receptor (CAR) is a component of the tight junction and is inaccessible to virus approaching from the apical surface. Many CVBs also interact with the GPI-anchored protein decay-accelerating factor (DAF). Here, we report that virus attachment to DAF on the apical cell surface activates Abl kinase, triggering Rac-dependent actin rearrangements that permit virus movement to the tight junction. Within the junction, interaction with CAR promotes conformational changes in the virus capsid that are essential for virus entry and release of viral RNA. Interaction with DAF also activates Fyn kinase, an event that is required for the phosphorylation of caveolin and transport of virus into the cell within caveolar vesicles. CVBs thus exploit DAF-mediated signaling pathways to surmount the epithelial barrier. |
doi_str_mv | 10.1016/j.cell.2005.10.035 |
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The coxsackievirus and adenovirus receptor (CAR) is a component of the tight junction and is inaccessible to virus approaching from the apical surface. Many CVBs also interact with the GPI-anchored protein decay-accelerating factor (DAF). Here, we report that virus attachment to DAF on the apical cell surface activates Abl kinase, triggering Rac-dependent actin rearrangements that permit virus movement to the tight junction. Within the junction, interaction with CAR promotes conformational changes in the virus capsid that are essential for virus entry and release of viral RNA. Interaction with DAF also activates Fyn kinase, an event that is required for the phosphorylation of caveolin and transport of virus into the cell within caveolar vesicles. 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The coxsackievirus and adenovirus receptor (CAR) is a component of the tight junction and is inaccessible to virus approaching from the apical surface. Many CVBs also interact with the GPI-anchored protein decay-accelerating factor (DAF). Here, we report that virus attachment to DAF on the apical cell surface activates Abl kinase, triggering Rac-dependent actin rearrangements that permit virus movement to the tight junction. Within the junction, interaction with CAR promotes conformational changes in the virus capsid that are essential for virus entry and release of viral RNA. Interaction with DAF also activates Fyn kinase, an event that is required for the phosphorylation of caveolin and transport of virus into the cell within caveolar vesicles. CVBs thus exploit DAF-mediated signaling pathways to surmount the epithelial barrier.</description><subject>Actins - physiology</subject><subject>Adenovirus</subject><subject>Caco-2 Cells</subject><subject>Caveolin 1 - metabolism</subject><subject>CD55 Antigens - metabolism</subject><subject>Coxsackievirus</subject><subject>Cytoskeleton - physiology</subject><subject>Cytoskeleton - virology</subject><subject>Enterovirus B, Human - metabolism</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - virology</subject><subject>Humans</subject><subject>Phosphorylation</subject><subject>Proto-Oncogene Proteins c-abl - metabolism</subject><subject>Proto-Oncogene Proteins c-fyn - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>src-Family Kinases - metabolism</subject><subject>Tight Junctions - physiology</subject><subject>Tight Junctions - virology</subject><subject>Tumor Cells, Cultured</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFPGzEUhC3UCgLtH-CAfOpt02evvfZKXFAUCi1SkaC9Wru2N3HYeIPtRc2_r1eJxK09vafRN3OYQeiSwJwAqb5u5tr2_ZwC8CzMoeQnaEagFgUjgn5AM4CaFrIS7Aydx7gBAMk5P0VnpGKkZLKaodVvF8ZY3HszamvwTdvjxht8u_f4h_NNtPjJrXzTR_xow9YlvBj-xEa_OPs2GfHSp7DHaR2GcbXGy51La9u7psfPbrVO-PvodXKDj5_Qxy6n2M_He4F-3S6fF3fFw89v94ubh0KzmqeCMEJlS0xHgLV1fkRHNRVcUC05M8xQIlnLoOxMRWrZQpVxTiU3suadbsoL9OWQuwvD62hjUlsXp5oab4cxKgGVZKLm_wWJYILQEjJID6AOQ4zBdmoX3LYJe0VATTuojZp8atph0vIO2XR1TB_brTXvlmPxGbg-ADaX8eZsUFE76_MGLlidlBncv_L_Am2imQk</recordid><startdate>20060113</startdate><enddate>20060113</enddate><creator>Coyne, Carolyn B.</creator><creator>Bergelson, Jeffrey M.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>20060113</creationdate><title>Virus-Induced Abl and Fyn Kinase Signals Permit Coxsackievirus Entry through Epithelial Tight Junctions</title><author>Coyne, Carolyn B. ; Bergelson, Jeffrey M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-14128b1df104b9b1d7f2c27572c854d4d2184b403fd6198b0628b5285d895fca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Actins - physiology</topic><topic>Adenovirus</topic><topic>Caco-2 Cells</topic><topic>Caveolin 1 - metabolism</topic><topic>CD55 Antigens - metabolism</topic><topic>Coxsackievirus</topic><topic>Cytoskeleton - physiology</topic><topic>Cytoskeleton - virology</topic><topic>Enterovirus B, Human - metabolism</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - virology</topic><topic>Humans</topic><topic>Phosphorylation</topic><topic>Proto-Oncogene Proteins c-abl - metabolism</topic><topic>Proto-Oncogene Proteins c-fyn - metabolism</topic><topic>Signal Transduction - physiology</topic><topic>src-Family Kinases - metabolism</topic><topic>Tight Junctions - physiology</topic><topic>Tight Junctions - virology</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Coyne, Carolyn B.</creatorcontrib><creatorcontrib>Bergelson, Jeffrey M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Coyne, Carolyn B.</au><au>Bergelson, Jeffrey M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Virus-Induced Abl and Fyn Kinase Signals Permit Coxsackievirus Entry through Epithelial Tight Junctions</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2006-01-13</date><risdate>2006</risdate><volume>124</volume><issue>1</issue><spage>119</spage><epage>131</epage><pages>119-131</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>Group B coxsackieviruses (CVBs) must cross the epithelium as they initiate infection, but the mechanism by which this occurs remains uncertain. 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subjects | Actins - physiology Adenovirus Caco-2 Cells Caveolin 1 - metabolism CD55 Antigens - metabolism Coxsackievirus Cytoskeleton - physiology Cytoskeleton - virology Enterovirus B, Human - metabolism Epithelial Cells - metabolism Epithelial Cells - virology Humans Phosphorylation Proto-Oncogene Proteins c-abl - metabolism Proto-Oncogene Proteins c-fyn - metabolism Signal Transduction - physiology src-Family Kinases - metabolism Tight Junctions - physiology Tight Junctions - virology Tumor Cells, Cultured |
title | Virus-Induced Abl and Fyn Kinase Signals Permit Coxsackievirus Entry through Epithelial Tight Junctions |
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