Rapamycin does not inhibit human cytomegalovirus reactivation from dendritic cells in vitro.
Identifieur interne : 000E25 ( Main/Exploration ); précédent : 000E24; suivant : 000E26Rapamycin does not inhibit human cytomegalovirus reactivation from dendritic cells in vitro.
Auteurs : Thomas E. Glover [Royaume-Uni] ; Verity G. Kew [Royaume-Uni] ; Matthew B. Reeves [Royaume-Uni]Source :
- The Journal of general virology [ 1465-2099 ] ; 2014.
Descripteurs français
- KwdFr :
- Activation virale (effets des médicaments et des substances chimiques), Antiviraux (pharmacologie), Cellules cultivées (MeSH), Cellules dendritiques (effets des médicaments et des substances chimiques), Cellules dendritiques (virologie), Cytomegalovirus (effets des médicaments et des substances chimiques), Cytomegalovirus (physiologie), Expression des gènes (effets des médicaments et des substances chimiques), Humains (MeSH), Sirolimus (pharmacologie).
- MESH :
- effets des médicaments et des substances chimiques : Activation virale, Cellules dendritiques, Cytomegalovirus, Expression des gènes.
- pharmacologie : Antiviraux, Sirolimus.
- physiologie : Cytomegalovirus.
- virologie : Cellules dendritiques.
- Cellules cultivées, Humains.
English descriptors
- KwdEn :
- MESH :
- chemical , pharmacology : Antiviral Agents, Sirolimus.
- drug effects : Cytomegalovirus, Dendritic Cells, Gene Expression, Virus Activation.
- physiology : Cytomegalovirus.
- virology : Dendritic Cells.
- Cells, Cultured, Humans.
Abstract
Human cytomegalovirus (HCMV) infection and reactivation are a major cause of morbidity in immune-suppressed patients. Interestingly, epidemiological studies have shown that patients administered the mammalian target of rapamycin (mTOR) inhibitor, sirolimus (rapamycin), exhibit more favourable outcomes, suggestive of activity against HCMV in vivo. Given its relative lack of activity against lytic infection, it is postulated that rapamycin inhibits HCMV reactivation. Here, we showed that rapamycin administered acutely or chronically has little impact on induction of immediate early (IE) gene expression in experimentally latent dendritic cells or cells from naturally latent individuals. Furthermore, we extended these observations to include other inhibitors of mTORC1 and mTORC 2, which similarly have minimal effects on induction of IE gene expression from latency. Taken together, these data suggest that favourable outcomes associated with sirolimus are attributable to indirect effects that influence HCMV reactivation, rather than a direct mechanistic action against HCMV itself.
DOI: 10.1099/vir.0.066332-0
PubMed: 24986086
PubMed Central: PMC4165932
Affiliations:
- Royaume-Uni
- Angleterre, Angleterre de l'Est, Grand Londres
- Cambridge, Londres
- University College de Londres, Université de Cambridge
Links toward previous steps (curation, corpus...)
Le document en format XML
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Glover</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Kew, Verity G" sort="Kew, Verity G" uniqKey="Kew V" first="Verity G" last="Kew">Verity G. 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Glover</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Kew, Verity G" sort="Kew, Verity G" uniqKey="Kew V" first="Verity G" last="Kew">Verity G. Kew</name><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author><author><name sortKey="Reeves, Matthew B" sort="Reeves, Matthew B" uniqKey="Reeves M" first="Matthew B" last="Reeves">Matthew B. Reeves</name><affiliation wicri:level="4"><nlm:affiliation>Institute of Immunity & Transplantation, Royal Free Hospital, University College London, Hampstead, London NW3 2PF, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Immunity & Transplantation, Royal Free Hospital, University College London, Hampstead, London NW3 2PF</wicri:regionArea><orgName type="university">University College de Londres</orgName><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ</wicri:regionArea><orgName type="university">Université de Cambridge</orgName><placeName><settlement type="city">Cambridge</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Angleterre de l'Est</region></placeName></affiliation></author></analytic><series><title level="j">The Journal of general virology</title><idno type="eISSN">1465-2099</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (pharmacology)</term><term>Cells, Cultured (MeSH)</term><term>Cytomegalovirus (drug effects)</term><term>Cytomegalovirus (physiology)</term><term>Dendritic Cells (drug effects)</term><term>Dendritic Cells (virology)</term><term>Gene Expression (drug effects)</term><term>Humans (MeSH)</term><term>Sirolimus (pharmacology)</term><term>Virus Activation (drug effects)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation virale (effets des médicaments et des substances chimiques)</term><term>Antiviraux (pharmacologie)</term><term>Cellules cultivées (MeSH)</term><term>Cellules dendritiques (effets des médicaments et des substances chimiques)</term><term>Cellules dendritiques (virologie)</term><term>Cytomegalovirus (effets des médicaments et des substances chimiques)</term><term>Cytomegalovirus (physiologie)</term><term>Expression des gènes (effets des médicaments et des substances chimiques)</term><term>Humains (MeSH)</term><term>Sirolimus (pharmacologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Sirolimus</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cytomegalovirus</term><term>Dendritic Cells</term><term>Gene Expression</term><term>Virus Activation</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Activation virale</term><term>Cellules dendritiques</term><term>Cytomegalovirus</term><term>Expression des gènes</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term><term>Sirolimus</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Cytomegalovirus</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Cytomegalovirus</term></keywords><keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Cellules dendritiques</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Dendritic Cells</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cells, Cultured</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Cellules cultivées</term><term>Humains</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Human cytomegalovirus (HCMV) infection and reactivation are a major cause of morbidity in immune-suppressed patients. Interestingly, epidemiological studies have shown that patients administered the mammalian target of rapamycin (mTOR) inhibitor, sirolimus (rapamycin), exhibit more favourable outcomes, suggestive of activity against HCMV in vivo. Given its relative lack of activity against lytic infection, it is postulated that rapamycin inhibits HCMV reactivation. Here, we showed that rapamycin administered acutely or chronically has little impact on induction of immediate early (IE) gene expression in experimentally latent dendritic cells or cells from naturally latent individuals. Furthermore, we extended these observations to include other inhibitors of mTORC1 and mTORC 2, which similarly have minimal effects on induction of IE gene expression from latency. Taken together, these data suggest that favourable outcomes associated with sirolimus are attributable to indirect effects that influence HCMV reactivation, rather than a direct mechanistic action against HCMV itself. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24986086</PMID><DateCompleted><Year>2014</Year><Month>11</Month><Day>10</Day></DateCompleted><DateRevised><Year>2020</Year><Month>10</Month><Day>27</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1465-2099</ISSN><JournalIssue CitedMedium="Internet"><Volume>95</Volume><Issue>Pt 10</Issue><PubDate><Year>2014</Year><Month>Oct</Month></PubDate></JournalIssue><Title>The Journal of general virology</Title><ISOAbbreviation>J Gen Virol</ISOAbbreviation></Journal><ArticleTitle>Rapamycin does not inhibit human cytomegalovirus reactivation from dendritic cells in vitro.</ArticleTitle><Pagination><MedlinePgn>2260-2266</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1099/vir.0.066332-0</ELocationID><Abstract><AbstractText>Human cytomegalovirus (HCMV) infection and reactivation are a major cause of morbidity in immune-suppressed patients. Interestingly, epidemiological studies have shown that patients administered the mammalian target of rapamycin (mTOR) inhibitor, sirolimus (rapamycin), exhibit more favourable outcomes, suggestive of activity against HCMV in vivo. Given its relative lack of activity against lytic infection, it is postulated that rapamycin inhibits HCMV reactivation. Here, we showed that rapamycin administered acutely or chronically has little impact on induction of immediate early (IE) gene expression in experimentally latent dendritic cells or cells from naturally latent individuals. Furthermore, we extended these observations to include other inhibitors of mTORC1 and mTORC 2, which similarly have minimal effects on induction of IE gene expression from latency. Taken together, these data suggest that favourable outcomes associated with sirolimus are attributable to indirect effects that influence HCMV reactivation, rather than a direct mechanistic action against HCMV itself. </AbstractText><CopyrightInformation>© 2014 The Authors.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Glover</LastName><ForeName>Thomas E</ForeName><Initials>TE</Initials><AffiliationInfo><Affiliation>Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kew</LastName><ForeName>Verity G</ForeName><Initials>VG</Initials><AffiliationInfo><Affiliation>Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Reeves</LastName><ForeName>Matthew B</ForeName><Initials>MB</Initials><AffiliationInfo><Affiliation>Institute of Immunity & Transplantation, Royal Free Hospital, University College London, Hampstead, London NW3 2PF, UK.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>G0900466</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant><Grant><GrantID>G:0900466</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>07</Month><Day>01</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>J Gen Virol</MedlineTA><NlmUniqueID>0077340</NlmUniqueID><ISSNLinking>0022-1317</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>W36ZG6FT64</RegistryNumber><NameOfSubstance UI="D020123">Sirolimus</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003587" MajorTopicYN="N">Cytomegalovirus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003713" MajorTopicYN="N">Dendritic Cells</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015870" MajorTopicYN="N">Gene Expression</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020123" MajorTopicYN="N">Sirolimus</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014775" MajorTopicYN="N">Virus Activation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>7</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>7</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>11</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">24986086</ArticleId><ArticleId IdType="doi">10.1099/vir.0.066332-0</ArticleId><ArticleId IdType="pmc">PMC4165932</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Angleterre de l'Est</li><li>Grand Londres</li></region><settlement><li>Cambridge</li><li>Londres</li></settlement><orgName><li>University College de Londres</li><li>Université de Cambridge</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Glover, Thomas E" sort="Glover, Thomas E" uniqKey="Glover T" first="Thomas E" last="Glover">Thomas E. Glover</name></region><name sortKey="Kew, Verity G" sort="Kew, Verity G" uniqKey="Kew V" first="Verity G" last="Kew">Verity G. Kew</name><name sortKey="Reeves, Matthew B" sort="Reeves, Matthew B" uniqKey="Reeves M" first="Matthew B" last="Reeves">Matthew B. Reeves</name><name sortKey="Reeves, Matthew B" sort="Reeves, Matthew B" uniqKey="Reeves M" first="Matthew B" last="Reeves">Matthew B. Reeves</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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