Inhibition of Theiler's virus-induced apoptosis in infected murine macrophages results in necroptosis
•Theiler's virus induces apoptosis in murine macrophages through the intrinsic pathway reducing virus yields late in infection.•Inhibition of apoptosis led to the induction of necroptosis, a programmed form of necrosis.•Signaling events preceding necroptosis included phosphorylation of receptor...
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| Veröffentlicht in: | Virus research 2015-01, Vol.195, p.177-182 |
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| creator | Son, Kyung-No Lipton, Howard L. |
| description | •Theiler's virus induces apoptosis in murine macrophages through the intrinsic pathway reducing virus yields late in infection.•Inhibition of apoptosis led to the induction of necroptosis, a programmed form of necrosis.•Signaling events preceding necroptosis included phosphorylation of receptor interacting protein 1 (RIP1) and localization of RIP1 and RIP3 to mitochondria.•Blocking both apoptosis and necroptosis restored virus yields.
In mice Theiler's murine encephalomyelitis virus (TMEV) persists in macrophages that eventually undergo apoptosis. TMEV infection of macrophages in culture induces apoptosis through the intrinsic pathway, restricting virus yields. We show that inhibition of TMEV-induced apoptosis leads to phosphorylation of receptor interacting protein 1 (RIP1), localization of RIP1 and RIP3 to mitochondria, ROS production independent of MAPK activation and programmed necrosis (necroptosis). Blocking both apoptosis and necroptosis restored virus yields. |
| doi_str_mv | 10.1016/j.virusres.2014.10.017 |
| format | Article |
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In mice Theiler's murine encephalomyelitis virus (TMEV) persists in macrophages that eventually undergo apoptosis. TMEV infection of macrophages in culture induces apoptosis through the intrinsic pathway, restricting virus yields. We show that inhibition of TMEV-induced apoptosis leads to phosphorylation of receptor interacting protein 1 (RIP1), localization of RIP1 and RIP3 to mitochondria, ROS production independent of MAPK activation and programmed necrosis (necroptosis). Blocking both apoptosis and necroptosis restored virus yields.</description><identifier>ISSN: 0168-1702</identifier><identifier>EISSN: 1872-7492</identifier><identifier>DOI: 10.1016/j.virusres.2014.10.017</identifier><identifier>PMID: 25449910</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Apoptosis ; Cardiovirus B ; Cell Death ; GTPase-Activating Proteins - metabolism ; Host-Pathogen Interactions ; macrophages ; Macrophages - physiology ; Macrophages - virology ; Mice ; mitochondria ; Mitochondria - chemistry ; mitogen-activated protein kinase ; Necroptosis ; Phosphorylation ; Protein Processing, Post-Translational ; Reactive Oxygen Species - metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases - metabolism ; RIP1 ; Theiler's encephalomyelitis virus ; Theiler's virus ; Theilovirus - physiology ; Viral Load ; Virus titers ; viruses</subject><ispartof>Virus research, 2015-01, Vol.195, p.177-182</ispartof><rights>2014 Elsevier B.V.</rights><rights>Copyright © 2014 Elsevier B.V. All rights reserved.</rights><rights>2014 Elsevier B.V. All rights reserved. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c537t-a6e95f3fb2530715e604cdf90f48a1aebb6ad46e7605a4a645ee1d29d28db6083</citedby><cites>FETCH-LOGICAL-c537t-a6e95f3fb2530715e604cdf90f48a1aebb6ad46e7605a4a645ee1d29d28db6083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.virusres.2014.10.017$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25449910$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Son, Kyung-No</creatorcontrib><creatorcontrib>Lipton, Howard L.</creatorcontrib><title>Inhibition of Theiler's virus-induced apoptosis in infected murine macrophages results in necroptosis</title><title>Virus research</title><addtitle>Virus Res</addtitle><description>•Theiler's virus induces apoptosis in murine macrophages through the intrinsic pathway reducing virus yields late in infection.•Inhibition of apoptosis led to the induction of necroptosis, a programmed form of necrosis.•Signaling events preceding necroptosis included phosphorylation of receptor interacting protein 1 (RIP1) and localization of RIP1 and RIP3 to mitochondria.•Blocking both apoptosis and necroptosis restored virus yields.
In mice Theiler's murine encephalomyelitis virus (TMEV) persists in macrophages that eventually undergo apoptosis. TMEV infection of macrophages in culture induces apoptosis through the intrinsic pathway, restricting virus yields. We show that inhibition of TMEV-induced apoptosis leads to phosphorylation of receptor interacting protein 1 (RIP1), localization of RIP1 and RIP3 to mitochondria, ROS production independent of MAPK activation and programmed necrosis (necroptosis). Blocking both apoptosis and necroptosis restored virus yields.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Cardiovirus B</subject><subject>Cell Death</subject><subject>GTPase-Activating Proteins - metabolism</subject><subject>Host-Pathogen Interactions</subject><subject>macrophages</subject><subject>Macrophages - physiology</subject><subject>Macrophages - virology</subject><subject>Mice</subject><subject>mitochondria</subject><subject>Mitochondria - chemistry</subject><subject>mitogen-activated protein kinase</subject><subject>Necroptosis</subject><subject>Phosphorylation</subject><subject>Protein Processing, Post-Translational</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Receptor-Interacting Protein Serine-Threonine Kinases - metabolism</subject><subject>RIP1</subject><subject>Theiler's encephalomyelitis virus</subject><subject>Theiler's virus</subject><subject>Theilovirus - physiology</subject><subject>Viral Load</subject><subject>Virus titers</subject><subject>viruses</subject><issn>0168-1702</issn><issn>1872-7492</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU9v1DAQxS0EotvCV6hyg0sW_4udXBCoAlqpEpdytpx40p1VYgc7WanfHme3reBUJEuWnt-8Gc-PkEtGt4wy9Wm_PWBcUoS05ZTJLG4p06_IhtWal1o2_DXZZGNdMk35GTlPaU8pVUKrt-SMV1I2DaMbAjd-hy3OGHwR-uJuBzhA_JCKY3yJ3i0duMJOYZpDwlSgz6eHbs7quET0UIy2i2Ha2XtIRR5oGeajzcMqH6vekTe9HRK8f7wvyK_v3-6ursvbnz9urr7ell0l9FxaBU3Vi77llaCaVaCo7Fzf0F7WllloW2WdVKAVray0SlYAzPHG8dq1itbignw-5U5LO4LrwM_RDmaKONr4YIJF8--Lx525DwcjBW2E0jng42NADL8XSLMZMXUwDNZDWJLhrBKKMaXki1amZN48rzn7D6uQmotarAOokzXvLmW8_fPwjJqVvNmbJ_JmJb_qmXwuvPz7689lT6iz4cvJABnAASGa1CH4TBdjxmlcwJd6_AG1OcYX</recordid><startdate>20150102</startdate><enddate>20150102</enddate><creator>Son, Kyung-No</creator><creator>Lipton, Howard L.</creator><general>Elsevier B.V</general><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>7X8</scope><scope>7U9</scope><scope>H94</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20150102</creationdate><title>Inhibition of Theiler's virus-induced apoptosis in infected murine macrophages results in necroptosis</title><author>Son, Kyung-No ; Lipton, Howard L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-a6e95f3fb2530715e604cdf90f48a1aebb6ad46e7605a4a645ee1d29d28db6083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Cardiovirus B</topic><topic>Cell Death</topic><topic>GTPase-Activating Proteins - metabolism</topic><topic>Host-Pathogen Interactions</topic><topic>macrophages</topic><topic>Macrophages - physiology</topic><topic>Macrophages - virology</topic><topic>Mice</topic><topic>mitochondria</topic><topic>Mitochondria - chemistry</topic><topic>mitogen-activated protein kinase</topic><topic>Necroptosis</topic><topic>Phosphorylation</topic><topic>Protein Processing, Post-Translational</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Receptor-Interacting Protein Serine-Threonine Kinases - metabolism</topic><topic>RIP1</topic><topic>Theiler's encephalomyelitis virus</topic><topic>Theiler's virus</topic><topic>Theilovirus - physiology</topic><topic>Viral Load</topic><topic>Virus titers</topic><topic>viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Son, Kyung-No</creatorcontrib><creatorcontrib>Lipton, Howard L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Virus research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Son, Kyung-No</au><au>Lipton, Howard L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Theiler's virus-induced apoptosis in infected murine macrophages results in necroptosis</atitle><jtitle>Virus research</jtitle><addtitle>Virus Res</addtitle><date>2015-01-02</date><risdate>2015</risdate><volume>195</volume><spage>177</spage><epage>182</epage><pages>177-182</pages><issn>0168-1702</issn><eissn>1872-7492</eissn><abstract>•Theiler's virus induces apoptosis in murine macrophages through the intrinsic pathway reducing virus yields late in infection.•Inhibition of apoptosis led to the induction of necroptosis, a programmed form of necrosis.•Signaling events preceding necroptosis included phosphorylation of receptor interacting protein 1 (RIP1) and localization of RIP1 and RIP3 to mitochondria.•Blocking both apoptosis and necroptosis restored virus yields.
In mice Theiler's murine encephalomyelitis virus (TMEV) persists in macrophages that eventually undergo apoptosis. TMEV infection of macrophages in culture induces apoptosis through the intrinsic pathway, restricting virus yields. We show that inhibition of TMEV-induced apoptosis leads to phosphorylation of receptor interacting protein 1 (RIP1), localization of RIP1 and RIP3 to mitochondria, ROS production independent of MAPK activation and programmed necrosis (necroptosis). Blocking both apoptosis and necroptosis restored virus yields.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25449910</pmid><doi>10.1016/j.virusres.2014.10.017</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Virus research, 2015-01, Vol.195, p.177-182 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Apoptosis Cardiovirus B Cell Death GTPase-Activating Proteins - metabolism Host-Pathogen Interactions macrophages Macrophages - physiology Macrophages - virology Mice mitochondria Mitochondria - chemistry mitogen-activated protein kinase Necroptosis Phosphorylation Protein Processing, Post-Translational Reactive Oxygen Species - metabolism Receptor-Interacting Protein Serine-Threonine Kinases - metabolism RIP1 Theiler's encephalomyelitis virus Theiler's virus Theilovirus - physiology Viral Load Virus titers viruses |
| title | Inhibition of Theiler's virus-induced apoptosis in infected murine macrophages results in necroptosis |
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