Up-regulation of Mcl-1 and Bak by coronavirus infection of human, avian and animal cells modulates apoptosis and viral replication
Virus-induced apoptosis and viral mechanisms that regulate this cell death program are key issues in understanding virus-host interactions and viral pathogenesis. Like many other human and animal viruses, coronavirus infection of mammalian cells induces apoptosis. In this study, the global gene expr...
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| Veröffentlicht in: | PloS one 2012-01, Vol.7 (1), p.e30191-e30191 |
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| creator | Zhong, Yanxin Liao, Ying Fang, Shouguo Tam, James P Liu, Ding Xiang |
| description | Virus-induced apoptosis and viral mechanisms that regulate this cell death program are key issues in understanding virus-host interactions and viral pathogenesis. Like many other human and animal viruses, coronavirus infection of mammalian cells induces apoptosis. In this study, the global gene expression profiles are first determined in IBV-infected Vero cells at 24 hours post-infection by Affymetrix array, using avian coronavirus infectious bronchitis virus (IBV) as a model system. It reveals an up-regulation at the transcriptional level of both pro-apoptotic Bak and pro-survival myeloid cell leukemia-1 (Mcl-1). These results were further confirmed both in vivo and in vitro, in IBV-infected embryonated chicken eggs, chicken fibroblast cells and mammalian cells at transcriptional and translational levels, respectively. Interestingly, the onset of apoptosis occurred earlier in IBV-infected mammalian cells silenced with short interfering RNA targeting Mcl-1 (siMcl-1), and was delayed in cells silenced with siBak. IBV progeny production and release were increased in infected Mcl-1 knockdown cells compared to similarly infected control cells, while the contrary was observed in infected Bak knockdown cells. Furthermore, IBV infection-induced up-regulation of GADD153 regulated the expression of Mcl-1. Inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) and phosphoinositide 3-kinase (PI3K/Akt) signaling pathways by chemical inhibitors and knockdown of GADD153 by siRNA demonstrated the involvement of ER-stress response in regulation of IBV-induced Mcl-1 expression. These results illustrate the sophisticated regulatory strategies evolved by a coronavirus to modulate both virus-induced apoptosis and viral replication during its replication cycle. |
| doi_str_mv | 10.1371/journal.pone.0030191 |
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Like many other human and animal viruses, coronavirus infection of mammalian cells induces apoptosis. In this study, the global gene expression profiles are first determined in IBV-infected Vero cells at 24 hours post-infection by Affymetrix array, using avian coronavirus infectious bronchitis virus (IBV) as a model system. It reveals an up-regulation at the transcriptional level of both pro-apoptotic Bak and pro-survival myeloid cell leukemia-1 (Mcl-1). These results were further confirmed both in vivo and in vitro, in IBV-infected embryonated chicken eggs, chicken fibroblast cells and mammalian cells at transcriptional and translational levels, respectively. Interestingly, the onset of apoptosis occurred earlier in IBV-infected mammalian cells silenced with short interfering RNA targeting Mcl-1 (siMcl-1), and was delayed in cells silenced with siBak. IBV progeny production and release were increased in infected Mcl-1 knockdown cells compared to similarly infected control cells, while the contrary was observed in infected Bak knockdown cells. Furthermore, IBV infection-induced up-regulation of GADD153 regulated the expression of Mcl-1. Inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) and phosphoinositide 3-kinase (PI3K/Akt) signaling pathways by chemical inhibitors and knockdown of GADD153 by siRNA demonstrated the involvement of ER-stress response in regulation of IBV-induced Mcl-1 expression. These results illustrate the sophisticated regulatory strategies evolved by a coronavirus to modulate both virus-induced apoptosis and viral replication during its replication cycle.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0030191</identifier><identifier>PMID: 22253918</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Adenoviruses ; AKT protein ; Animals ; Apoptosis ; Apoptosis - genetics ; BAK protein ; bcl-2 Homologous Antagonist-Killer Protein - genetics ; bcl-2 Homologous Antagonist-Killer Protein - metabolism ; Biology ; Bronchitis ; Cancer ; Cell cycle ; Cell death ; Cell survival ; Cells (Biology) ; Cellular stress response ; Cercopithecus aethiops ; Chick Embryo ; Chickens - virology ; Chlamydia ; Chlamydia trachomatis ; CHOP protein ; Coronaviridae ; Coronavirus ; Coronavirus Infections - genetics ; Coronavirus Infections - virology ; Coronaviruses ; Cytochrome ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; Down-Regulation - genetics ; Eggs ; Endoplasmic reticulum ; Extracellular signal-regulated kinase ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Fibroblasts ; Fibroblasts - metabolism ; Fibroblasts - virology ; Gene expression ; Gene Knockdown Techniques ; Gene regulation ; Genes ; Health aspects ; Humans ; Infection ; Infections ; Infectious bronchitis virus ; Kinases ; Leukemia ; Mammalian cells ; Mammals ; Mcl-1 protein ; Melanoma ; Myeloid Cell Leukemia Sequence 1 Protein ; Myeloid cells ; Oligonucleotide Array Sequence Analysis ; Pathogenesis ; Phosphatidylinositol 3-Kinases - metabolism ; phosphoinositides ; Poly(ADP-ribose) Polymerases - metabolism ; Progeny ; Protein Biosynthesis ; Protein synthesis ; Proteins ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Regulations ; Replication ; Respiratory tract diseases ; Ribonucleic acid ; RNA ; RNA Interference ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Signal transduction ; Signaling ; siRNA ; Transcription ; Transcription Factor CHOP - metabolism ; Transcription, Genetic ; Translation ; Tumor necrosis factor-TNF ; Tumors ; Up-regulation ; Up-Regulation - genetics ; Vero Cells ; Virus replication ; Virus Replication - physiology ; Viruses</subject><ispartof>PloS one, 2012-01, Vol.7 (1), p.e30191-e30191</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Zhong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Zhong et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c789t-f5ab1f2ef47cf8fe7badcdfdb5c948a5ab658174460f4d2ef7c10155f8d296933</citedby><cites>FETCH-LOGICAL-c789t-f5ab1f2ef47cf8fe7badcdfdb5c948a5ab658174460f4d2ef7c10155f8d296933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256233/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256233/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22253918$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kim, Baek</contributor><creatorcontrib>Zhong, Yanxin</creatorcontrib><creatorcontrib>Liao, Ying</creatorcontrib><creatorcontrib>Fang, Shouguo</creatorcontrib><creatorcontrib>Tam, James P</creatorcontrib><creatorcontrib>Liu, Ding Xiang</creatorcontrib><title>Up-regulation of Mcl-1 and Bak by coronavirus infection of human, avian and animal cells modulates apoptosis and viral replication</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Virus-induced apoptosis and viral mechanisms that regulate this cell death program are key issues in understanding virus-host interactions and viral pathogenesis. Like many other human and animal viruses, coronavirus infection of mammalian cells induces apoptosis. In this study, the global gene expression profiles are first determined in IBV-infected Vero cells at 24 hours post-infection by Affymetrix array, using avian coronavirus infectious bronchitis virus (IBV) as a model system. It reveals an up-regulation at the transcriptional level of both pro-apoptotic Bak and pro-survival myeloid cell leukemia-1 (Mcl-1). These results were further confirmed both in vivo and in vitro, in IBV-infected embryonated chicken eggs, chicken fibroblast cells and mammalian cells at transcriptional and translational levels, respectively. Interestingly, the onset of apoptosis occurred earlier in IBV-infected mammalian cells silenced with short interfering RNA targeting Mcl-1 (siMcl-1), and was delayed in cells silenced with siBak. IBV progeny production and release were increased in infected Mcl-1 knockdown cells compared to similarly infected control cells, while the contrary was observed in infected Bak knockdown cells. Furthermore, IBV infection-induced up-regulation of GADD153 regulated the expression of Mcl-1. Inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) and phosphoinositide 3-kinase (PI3K/Akt) signaling pathways by chemical inhibitors and knockdown of GADD153 by siRNA demonstrated the involvement of ER-stress response in regulation of IBV-induced Mcl-1 expression. These results illustrate the sophisticated regulatory strategies evolved by a coronavirus to modulate both virus-induced apoptosis and viral replication during its replication cycle.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Adenoviruses</subject><subject>AKT protein</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - genetics</subject><subject>BAK protein</subject><subject>bcl-2 Homologous Antagonist-Killer Protein - genetics</subject><subject>bcl-2 Homologous Antagonist-Killer Protein - metabolism</subject><subject>Biology</subject><subject>Bronchitis</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cell death</subject><subject>Cell survival</subject><subject>Cells (Biology)</subject><subject>Cellular stress response</subject><subject>Cercopithecus aethiops</subject><subject>Chick Embryo</subject><subject>Chickens - virology</subject><subject>Chlamydia</subject><subject>Chlamydia trachomatis</subject><subject>CHOP protein</subject><subject>Coronaviridae</subject><subject>Coronavirus</subject><subject>Coronavirus Infections - genetics</subject><subject>Coronavirus Infections - virology</subject><subject>Coronaviruses</subject><subject>Cytochrome</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Down-Regulation - genetics</subject><subject>Eggs</subject><subject>Endoplasmic reticulum</subject><subject>Extracellular signal-regulated kinase</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Fibroblasts</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - virology</subject><subject>Gene expression</subject><subject>Gene Knockdown Techniques</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infection</subject><subject>Infections</subject><subject>Infectious bronchitis virus</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Mammalian cells</subject><subject>Mammals</subject><subject>Mcl-1 protein</subject><subject>Melanoma</subject><subject>Myeloid Cell Leukemia Sequence 1 Protein</subject><subject>Myeloid cells</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Pathogenesis</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>phosphoinositides</subject><subject>Poly(ADP-ribose) Polymerases - metabolism</subject><subject>Progeny</subject><subject>Protein Biosynthesis</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Regulations</subject><subject>Replication</subject><subject>Respiratory tract diseases</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Interference</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>siRNA</subject><subject>Transcription</subject><subject>Transcription Factor CHOP - metabolism</subject><subject>Transcription, Genetic</subject><subject>Translation</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumors</subject><subject>Up-regulation</subject><subject>Up-Regulation - genetics</subject><subject>Vero Cells</subject><subject>Virus replication</subject><subject>Virus Replication - physiology</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLC4pgx3y3vRHWxY-BlQV1vQ1pmsxkTJuatIt76y83neksU9mLpRcpOc95k_OenCR5DsEC4hy-27jBt8IuOteqBQAYwBI-SI5hiVHGEMAPD_6PkichbACguGDscXKEEKK4hMVx8veqy7xaDVb0xrWp0-lXaTOYirZOP4hfaXWTSuddK66NH0JqWq3knlwPjWjfpjEk2m2CaE0jbCqVtSFtXD2qqpCKznW9CyZsoSgUGa86a-T20KfJIy1sUM-m9SS5-vTxx_mX7OLy8_L87CKTeVH2maaighopTXKpC63yStSy1nVFZUkKEaOMFjAnhAFN6sjlEgJIqS5qVLIS45Pk5U63sy7wyb7AIUaIlIgAFInljqid2PDOx2r8DXfC8O2G8ysufG-kVVxAiAATEirKCMKwQhQhLDXEQNXR5qj1fjptqBpVS9X2se6Z6DzSmjVfuWuOEWUIj9d9PQl493tQoeeNCaO1olVuCLykhNEcknuQkBWUYFRG8vQ_8m4bJmolYqWx5S5eUI6a_IzkOWQ5RSRSizuo-NWqMTI-Sm3i_izhzSwhMr3606_EEAJffv92f_by55x9dcCulbD9Ojg7jG8rzEGyA6V3IXilb7sBAR9nau8GH2eKTzMV014cdvI2aT9E-B_yFRyS</recordid><startdate>20120111</startdate><enddate>20120111</enddate><creator>Zhong, Yanxin</creator><creator>Liao, Ying</creator><creator>Fang, Shouguo</creator><creator>Tam, James P</creator><creator>Liu, Ding Xiang</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>COVID</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120111</creationdate><title>Up-regulation of Mcl-1 and Bak by coronavirus infection of human, avian and animal cells modulates apoptosis and viral replication</title><author>Zhong, Yanxin ; Liao, Ying ; Fang, Shouguo ; Tam, James P ; Liu, Ding Xiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c789t-f5ab1f2ef47cf8fe7badcdfdb5c948a5ab658174460f4d2ef7c10155f8d296933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Adenoviruses</topic><topic>AKT protein</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - genetics</topic><topic>BAK protein</topic><topic>bcl-2 Homologous Antagonist-Killer Protein - genetics</topic><topic>bcl-2 Homologous Antagonist-Killer Protein - metabolism</topic><topic>Biology</topic><topic>Bronchitis</topic><topic>Cancer</topic><topic>Cell cycle</topic><topic>Cell death</topic><topic>Cell survival</topic><topic>Cells (Biology)</topic><topic>Cellular stress response</topic><topic>Cercopithecus aethiops</topic><topic>Chick Embryo</topic><topic>Chickens - virology</topic><topic>Chlamydia</topic><topic>Chlamydia trachomatis</topic><topic>CHOP protein</topic><topic>Coronaviridae</topic><topic>Coronavirus</topic><topic>Coronavirus Infections - genetics</topic><topic>Coronavirus Infections - virology</topic><topic>Coronaviruses</topic><topic>Cytochrome</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Down-Regulation - genetics</topic><topic>Eggs</topic><topic>Endoplasmic reticulum</topic><topic>Extracellular signal-regulated kinase</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Fibroblasts</topic><topic>Fibroblasts - metabolism</topic><topic>Fibroblasts - virology</topic><topic>Gene expression</topic><topic>Gene Knockdown Techniques</topic><topic>Gene regulation</topic><topic>Genes</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Infection</topic><topic>Infections</topic><topic>Infectious bronchitis virus</topic><topic>Kinases</topic><topic>Leukemia</topic><topic>Mammalian cells</topic><topic>Mammals</topic><topic>Mcl-1 protein</topic><topic>Melanoma</topic><topic>Myeloid Cell Leukemia Sequence 1 Protein</topic><topic>Myeloid cells</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Pathogenesis</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>phosphoinositides</topic><topic>Poly(ADP-ribose) Polymerases - metabolism</topic><topic>Progeny</topic><topic>Protein Biosynthesis</topic><topic>Protein synthesis</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Regulations</topic><topic>Replication</topic><topic>Respiratory tract diseases</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA Interference</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>siRNA</topic><topic>Transcription</topic><topic>Transcription Factor CHOP - metabolism</topic><topic>Transcription, Genetic</topic><topic>Translation</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumors</topic><topic>Up-regulation</topic><topic>Up-Regulation - genetics</topic><topic>Vero Cells</topic><topic>Virus replication</topic><topic>Virus Replication - physiology</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhong, Yanxin</creatorcontrib><creatorcontrib>Liao, Ying</creatorcontrib><creatorcontrib>Fang, Shouguo</creatorcontrib><creatorcontrib>Tam, James P</creatorcontrib><creatorcontrib>Liu, Ding Xiang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhong, Yanxin</au><au>Liao, Ying</au><au>Fang, Shouguo</au><au>Tam, James P</au><au>Liu, Ding Xiang</au><au>Kim, Baek</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Up-regulation of Mcl-1 and Bak by coronavirus infection of human, avian and animal cells modulates apoptosis and viral replication</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-01-11</date><risdate>2012</risdate><volume>7</volume><issue>1</issue><spage>e30191</spage><epage>e30191</epage><pages>e30191-e30191</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Virus-induced apoptosis and viral mechanisms that regulate this cell death program are key issues in understanding virus-host interactions and viral pathogenesis. Like many other human and animal viruses, coronavirus infection of mammalian cells induces apoptosis. In this study, the global gene expression profiles are first determined in IBV-infected Vero cells at 24 hours post-infection by Affymetrix array, using avian coronavirus infectious bronchitis virus (IBV) as a model system. It reveals an up-regulation at the transcriptional level of both pro-apoptotic Bak and pro-survival myeloid cell leukemia-1 (Mcl-1). These results were further confirmed both in vivo and in vitro, in IBV-infected embryonated chicken eggs, chicken fibroblast cells and mammalian cells at transcriptional and translational levels, respectively. Interestingly, the onset of apoptosis occurred earlier in IBV-infected mammalian cells silenced with short interfering RNA targeting Mcl-1 (siMcl-1), and was delayed in cells silenced with siBak. IBV progeny production and release were increased in infected Mcl-1 knockdown cells compared to similarly infected control cells, while the contrary was observed in infected Bak knockdown cells. Furthermore, IBV infection-induced up-regulation of GADD153 regulated the expression of Mcl-1. Inhibition of the mitogen-activated protein/extracellular signal-regulated kinase (MEK/ERK) and phosphoinositide 3-kinase (PI3K/Akt) signaling pathways by chemical inhibitors and knockdown of GADD153 by siRNA demonstrated the involvement of ER-stress response in regulation of IBV-induced Mcl-1 expression. These results illustrate the sophisticated regulatory strategies evolved by a coronavirus to modulate both virus-induced apoptosis and viral replication during its replication cycle.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22253918</pmid><doi>10.1371/journal.pone.0030191</doi><tpages>e30191</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-01, Vol.7 (1), p.e30191-e30191 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1322492402 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase Adenoviruses AKT protein Animals Apoptosis Apoptosis - genetics BAK protein bcl-2 Homologous Antagonist-Killer Protein - genetics bcl-2 Homologous Antagonist-Killer Protein - metabolism Biology Bronchitis Cancer Cell cycle Cell death Cell survival Cells (Biology) Cellular stress response Cercopithecus aethiops Chick Embryo Chickens - virology Chlamydia Chlamydia trachomatis CHOP protein Coronaviridae Coronavirus Coronavirus Infections - genetics Coronavirus Infections - virology Coronaviruses Cytochrome Cytotoxicity Deoxyribonucleic acid DNA Down-Regulation - genetics Eggs Endoplasmic reticulum Extracellular signal-regulated kinase Extracellular Signal-Regulated MAP Kinases - metabolism Fibroblasts Fibroblasts - metabolism Fibroblasts - virology Gene expression Gene Knockdown Techniques Gene regulation Genes Health aspects Humans Infection Infections Infectious bronchitis virus Kinases Leukemia Mammalian cells Mammals Mcl-1 protein Melanoma Myeloid Cell Leukemia Sequence 1 Protein Myeloid cells Oligonucleotide Array Sequence Analysis Pathogenesis Phosphatidylinositol 3-Kinases - metabolism phosphoinositides Poly(ADP-ribose) Polymerases - metabolism Progeny Protein Biosynthesis Protein synthesis Proteins Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Regulations Replication Respiratory tract diseases Ribonucleic acid RNA RNA Interference RNA, Messenger - genetics RNA, Messenger - metabolism Signal transduction Signaling siRNA Transcription Transcription Factor CHOP - metabolism Transcription, Genetic Translation Tumor necrosis factor-TNF Tumors Up-regulation Up-Regulation - genetics Vero Cells Virus replication Virus Replication - physiology Viruses |
| title | Up-regulation of Mcl-1 and Bak by coronavirus infection of human, avian and animal cells modulates apoptosis and viral replication |
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