RapamycinFungusV1, Main, Exploration, bibRecord, 000576

Induction of autophagy by PI3K/MTOR and PI3K/MTOR/BRD4 inhibitors suppresses HIV-1 replication.

Identifieur interne : 000576 ( Main/Exploration ); précédent : 000575; suivant : 000577

Induction of autophagy by PI3K/MTOR and PI3K/MTOR/BRD4 inhibitors suppresses HIV-1 replication.

Auteurs : Grant R. Campbell [États-Unis] ; Rachel S. Bruckman [États-Unis] ; Shayna D. Herns [États-Unis] ; Shweta Joshi [États-Unis] ; Donald L. Durden [États-Unis] ; Stephen A. Spector [États-Unis]

Source :

The Journal of biological chemistry [ 1083-351X ] ; 2018.

RBID : pubmed:29475942

Descripteurs français

KwdFr :
- Agents antiVIH (pharmacologie), Autophagie (effets des médicaments et des substances chimiques), Azépines (pharmacologie), Cellules cultivées (MeSH), Facteurs de transcription (antagonistes et inhibiteurs), Facteurs de transcription (métabolisme), Humains (MeSH), Imidazoles (pharmacologie), Infections à VIH (anatomopathologie), Infections à VIH (métabolisme), Infections à VIH (traitement médicamenteux), Infections à VIH (virologie), Inhibiteurs de protéines kinases (pharmacologie), Macrophages (anatomopathologie), Macrophages (effets des médicaments et des substances chimiques), Macrophages (métabolisme), Macrophages (virologie), Phosphatidylinositol 3-kinase (métabolisme), Protéines du cycle cellulaire (MeSH), Protéines nucléaires (antagonistes et inhibiteurs), Protéines nucléaires (métabolisme), Quinoléines (pharmacologie), Réplication virale (effets des médicaments et des substances chimiques), Sérine-thréonine kinases TOR (antagonistes et inhibiteurs), Sérine-thréonine kinases TOR (métabolisme), Transduction du signal (effets des médicaments et des substances chimiques), Triazoles (pharmacologie), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (effets des médicaments et des substances chimiques), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (physiologie).
MESH :
- anatomopathologie : Infections à VIH, Macrophages.
- antagonistes et inhibiteurs : Facteurs de transcription, Protéines nucléaires, Sérine-thréonine kinases TOR.
- effets des médicaments et des substances chimiques : Autophagie, Macrophages, Réplication virale, Transduction du signal, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- métabolisme : Facteurs de transcription, Infections à VIH, Macrophages, Phosphatidylinositol 3-kinase, Protéines nucléaires, Sérine-thréonine kinases TOR.
- pharmacologie : Agents antiVIH, Azépines, Imidazoles, Inhibiteurs de protéines kinases, Quinoléines, Triazoles.
- physiologie : VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- traitement médicamenteux : Infections à VIH.
- virologie : Infections à VIH, Macrophages.
- Cellules cultivées, Humains, Protéines du cycle cellulaire.

English descriptors

KwdEn :
- Anti-HIV Agents (pharmacology), Autophagy (drug effects), Azepines (pharmacology), Cell Cycle Proteins (MeSH), Cells, Cultured (MeSH), HIV Infections (drug therapy), HIV Infections (metabolism), HIV Infections (pathology), HIV Infections (virology), HIV-1 (drug effects), HIV-1 (physiology), Humans (MeSH), Imidazoles (pharmacology), Macrophages (drug effects), Macrophages (metabolism), Macrophages (pathology), Macrophages (virology), Nuclear Proteins (antagonists & inhibitors), Nuclear Proteins (metabolism), Phosphatidylinositol 3-Kinase (metabolism), Phosphoinositide-3 Kinase Inhibitors (MeSH), Protein Kinase Inhibitors (pharmacology), Quinolines (pharmacology), Signal Transduction (drug effects), TOR Serine-Threonine Kinases (antagonists & inhibitors), TOR Serine-Threonine Kinases (metabolism), Transcription Factors (antagonists & inhibitors), Transcription Factors (metabolism), Triazoles (pharmacology), Virus Replication (drug effects).
MESH :
- chemical , antagonists & inhibitors : Nuclear Proteins, TOR Serine-Threonine Kinases, Transcription Factors.
- chemical , metabolism : Nuclear Proteins, Phosphatidylinositol 3-Kinase, TOR Serine-Threonine Kinases, Transcription Factors.
- chemical , pharmacology : Anti-HIV Agents, Azepines, Imidazoles, Protein Kinase Inhibitors, Quinolines, Triazoles.
- drug effects : Autophagy, HIV-1, Macrophages, Signal Transduction, Virus Replication.
- drug therapy : HIV Infections.
- metabolism : HIV Infections, Macrophages.
- pathology : HIV Infections, Macrophages.
- physiology : HIV-1.
- virology : HIV Infections, Macrophages.
- chemical : Cell Cycle Proteins, Cells, Cultured, Humans, Phosphoinositide-3 Kinase Inhibitors.

Abstract

In this study, we investigated the effects of the dual phosphatidylinositol 3-kinase/mechanistic target of rapamycin (PI3K/MTOR) inhibitor dactolisib (NVP-BEZ235), the PI3K/MTOR/bromodomain-containing protein 4 (BRD4) inhibitor SF2523, and the bromodomain and extra terminal domain inhibitor JQ1 on the productive infection of primary macrophages with human immunodeficiency type-1 (HIV). These inhibitors did not alter the initial susceptibility of macrophages to HIV infection. However, dactolisib, JQ1, and SF2523 all decreased HIV replication in macrophages in a dose-dependent manner via degradation of intracellular HIV through autophagy. Macrophages treated with dactolisib, JQ1, or SF2523 displayed an increase in LC3B lipidation combined with SQSTM1 degradation without inducing increased cell death. LC3B-II levels were further increased in the presence of pepstatin A suggesting that these inhibitors induce autophagic flux. RNA interference for ATG5 and ATG7 and pharmacological inhibitors of autophagosome-lysosome fusion and of lysosomal hydrolases all blocked the inhibition of HIV. Thus, we demonstrate that the mechanism of PI3K/MTOR and PI3K/MTOR/BRD4 inhibitor suppression of HIV requires the formation of autophagosomes, as well as their subsequent maturation into autolysosomes. These data provide further evidence in support of a role for autophagy in the control of HIV infection and open new avenues for the use of this class of drugs in HIV therapy.

DOI: 10.1074/jbc.RA118.002353
PubMed: 29475942
PubMed Central: PMC5912471

Affiliations:

Links toward previous steps (curation, corpus...)

to stream Main, to step Corpus: 000607
to stream Main, to step Curation: 000607

Le document en format XML

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<country xml:lang="fr">États-Unis</country>
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<country xml:lang="fr">États-Unis</country>
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<series><title level="j">The Journal of biological chemistry</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Anti-HIV Agents (pharmacology)</term>
<term>Autophagy (drug effects)</term>
<term>Azepines (pharmacology)</term>
<term>Cell Cycle Proteins (MeSH)</term>
<term>Cells, Cultured (MeSH)</term>
<term>HIV Infections (drug therapy)</term>
<term>HIV Infections (metabolism)</term>
<term>HIV Infections (pathology)</term>
<term>HIV Infections (virology)</term>
<term>HIV-1 (drug effects)</term>
<term>HIV-1 (physiology)</term>
<term>Humans (MeSH)</term>
<term>Imidazoles (pharmacology)</term>
<term>Macrophages (drug effects)</term>
<term>Macrophages (metabolism)</term>
<term>Macrophages (pathology)</term>
<term>Macrophages (virology)</term>
<term>Nuclear Proteins (antagonists & inhibitors)</term>
<term>Nuclear Proteins (metabolism)</term>
<term>Phosphatidylinositol 3-Kinase (metabolism)</term>
<term>Phosphoinositide-3 Kinase Inhibitors (MeSH)</term>
<term>Protein Kinase Inhibitors (pharmacology)</term>
<term>Quinolines (pharmacology)</term>
<term>Signal Transduction (drug effects)</term>
<term>TOR Serine-Threonine Kinases (antagonists & inhibitors)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
<term>Transcription Factors (antagonists & inhibitors)</term>
<term>Transcription Factors (metabolism)</term>
<term>Triazoles (pharmacology)</term>
<term>Virus Replication (drug effects)</term>
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<term>Autophagie (effets des médicaments et des substances chimiques)</term>
<term>Azépines (pharmacologie)</term>
<term>Cellules cultivées (MeSH)</term>
<term>Facteurs de transcription (antagonistes et inhibiteurs)</term>
<term>Facteurs de transcription (métabolisme)</term>
<term>Humains (MeSH)</term>
<term>Imidazoles (pharmacologie)</term>
<term>Infections à VIH (anatomopathologie)</term>
<term>Infections à VIH (métabolisme)</term>
<term>Infections à VIH (traitement médicamenteux)</term>
<term>Infections à VIH (virologie)</term>
<term>Inhibiteurs de protéines kinases (pharmacologie)</term>
<term>Macrophages (anatomopathologie)</term>
<term>Macrophages (effets des médicaments et des substances chimiques)</term>
<term>Macrophages (métabolisme)</term>
<term>Macrophages (virologie)</term>
<term>Phosphatidylinositol 3-kinase (métabolisme)</term>
<term>Protéines du cycle cellulaire (MeSH)</term>
<term>Protéines nucléaires (antagonistes et inhibiteurs)</term>
<term>Protéines nucléaires (métabolisme)</term>
<term>Quinoléines (pharmacologie)</term>
<term>Réplication virale (effets des médicaments et des substances chimiques)</term>
<term>Sérine-thréonine kinases TOR (antagonistes et inhibiteurs)</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
<term>Transduction du signal (effets des médicaments et des substances chimiques)</term>
<term>Triazoles (pharmacologie)</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (effets des médicaments et des substances chimiques)</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (physiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Nuclear Proteins</term>
<term>TOR Serine-Threonine Kinases</term>
<term>Transcription Factors</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Nuclear Proteins</term>
<term>Phosphatidylinositol 3-Kinase</term>
<term>TOR Serine-Threonine Kinases</term>
<term>Transcription Factors</term>
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<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-HIV Agents</term>
<term>Azepines</term>
<term>Imidazoles</term>
<term>Protein Kinase Inhibitors</term>
<term>Quinolines</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Infections à VIH</term>
<term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Facteurs de transcription</term>
<term>Protéines nucléaires</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Autophagy</term>
<term>HIV-1</term>
<term>Macrophages</term>
<term>Signal Transduction</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>HIV Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Autophagie</term>
<term>Macrophages</term>
<term>Réplication virale</term>
<term>Transduction du signal</term>
<term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>HIV Infections</term>
<term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteurs de transcription</term>
<term>Infections à VIH</term>
<term>Macrophages</term>
<term>Phosphatidylinositol 3-kinase</term>
<term>Protéines nucléaires</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>HIV Infections</term>
<term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Agents antiVIH</term>
<term>Azépines</term>
<term>Imidazoles</term>
<term>Inhibiteurs de protéines kinases</term>
<term>Quinoléines</term>
<term>Triazoles</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>VIH-1 (Virus de l'Immunodéficience Humaine de type 1)</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>HIV-1</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Infections à VIH</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Infections à VIH</term>
<term>Macrophages</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>HIV Infections</term>
<term>Macrophages</term>
</keywords>
<keywords scheme="MESH" type="chemical" xml:lang="en"><term>Cell Cycle Proteins</term>
<term>Cells, Cultured</term>
<term>Humans</term>
<term>Phosphoinositide-3 Kinase Inhibitors</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Cellules cultivées</term>
<term>Humains</term>
<term>Protéines du cycle cellulaire</term>
</keywords>
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<front><div type="abstract" xml:lang="en">In this study, we investigated the effects of the dual phosphatidylinositol 3-kinase/mechanistic target of rapamycin (PI3K/MTOR) inhibitor dactolisib (NVP-BEZ235), the PI3K/MTOR/bromodomain-containing protein 4 (BRD4) inhibitor SF2523, and the bromodomain and extra terminal domain inhibitor JQ1 on the productive infection of primary macrophages with human immunodeficiency type-1 (HIV). These inhibitors did not alter the initial susceptibility of macrophages to HIV infection. However, dactolisib, JQ1, and SF2523 all decreased HIV replication in macrophages in a dose-dependent manner via degradation of intracellular HIV through autophagy. Macrophages treated with dactolisib, JQ1, or SF2523 displayed an increase in LC3B lipidation combined with SQSTM1 degradation without inducing increased cell death. LC3B-II levels were further increased in the presence of pepstatin A suggesting that these inhibitors induce autophagic flux. RNA interference for <i>ATG5</i>
 and <i>ATG7</i>
 and pharmacological inhibitors of autophagosome-lysosome fusion and of lysosomal hydrolases all blocked the inhibition of HIV. Thus, we demonstrate that the mechanism of PI3K/MTOR and PI3K/MTOR/BRD4 inhibitor suppression of HIV requires the formation of autophagosomes, as well as their subsequent maturation into autolysosomes. These data provide further evidence in support of a role for autophagy in the control of HIV infection and open new avenues for the use of this class of drugs in HIV therapy.</div>
</front>
</TEI>
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<DateCompleted><Year>2019</Year>
<Month>01</Month>
<Day>08</Day>
</DateCompleted>
<DateRevised><Year>2019</Year>
<Month>12</Month>
<Day>10</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1083-351X</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>293</Volume>
<Issue>16</Issue>
<PubDate><Year>2018</Year>
<Month>04</Month>
<Day>20</Day>
</PubDate>
</JournalIssue>
<Title>The Journal of biological chemistry</Title>
<ISOAbbreviation>J Biol Chem</ISOAbbreviation>
</Journal>
<ArticleTitle>Induction of autophagy by PI3K/MTOR and PI3K/MTOR/BRD4 inhibitors suppresses HIV-1 replication.</ArticleTitle>
<Pagination><MedlinePgn>5808-5820</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1074/jbc.RA118.002353</ELocationID>
<Abstract><AbstractText>In this study, we investigated the effects of the dual phosphatidylinositol 3-kinase/mechanistic target of rapamycin (PI3K/MTOR) inhibitor dactolisib (NVP-BEZ235), the PI3K/MTOR/bromodomain-containing protein 4 (BRD4) inhibitor SF2523, and the bromodomain and extra terminal domain inhibitor JQ1 on the productive infection of primary macrophages with human immunodeficiency type-1 (HIV). These inhibitors did not alter the initial susceptibility of macrophages to HIV infection. However, dactolisib, JQ1, and SF2523 all decreased HIV replication in macrophages in a dose-dependent manner via degradation of intracellular HIV through autophagy. Macrophages treated with dactolisib, JQ1, or SF2523 displayed an increase in LC3B lipidation combined with SQSTM1 degradation without inducing increased cell death. LC3B-II levels were further increased in the presence of pepstatin A suggesting that these inhibitors induce autophagic flux. RNA interference for <i>ATG5</i>
 and <i>ATG7</i>
 and pharmacological inhibitors of autophagosome-lysosome fusion and of lysosomal hydrolases all blocked the inhibition of HIV. Thus, we demonstrate that the mechanism of PI3K/MTOR and PI3K/MTOR/BRD4 inhibitor suppression of HIV requires the formation of autophagosomes, as well as their subsequent maturation into autolysosomes. These data provide further evidence in support of a role for autophagy in the control of HIV infection and open new avenues for the use of this class of drugs in HIV therapy.</AbstractText>
<CopyrightInformation>© 2018 Campbell et al.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Campbell</LastName>
<ForeName>Grant R</ForeName>
<Initials>GR</Initials>
<AffiliationInfo><Affiliation>From the Division of Infectious Diseases, Department of Pediatrics, University of California San Diego, La Jolla, California 92093-0672.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bruckman</LastName>
<ForeName>Rachel S</ForeName>
<Initials>RS</Initials>
<AffiliationInfo><Affiliation>From the Division of Infectious Diseases, Department of Pediatrics, University of California San Diego, La Jolla, California 92093-0672.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Herns</LastName>
<ForeName>Shayna D</ForeName>
<Initials>SD</Initials>
<AffiliationInfo><Affiliation>From the Division of Infectious Diseases, Department of Pediatrics, University of California San Diego, La Jolla, California 92093-0672.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Joshi</LastName>
<ForeName>Shweta</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>the Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California San Diego, La Jolla, California 92093-0819.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>the Rady Children's Hospital, San Diego, California 92123, and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Durden</LastName>
<ForeName>Donald L</ForeName>
<Initials>DL</Initials>
<AffiliationInfo><Affiliation>the Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California San Diego, La Jolla, California 92093-0819.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>the Rady Children's Hospital, San Diego, California 92123, and.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>SignalRx Pharmaceuticals, Inc., San Diego, California 92130.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Spector</LastName>
<ForeName>Stephen A</ForeName>
<Initials>SA</Initials>
<AffiliationInfo><Affiliation>From the Division of Infectious Diseases, Department of Pediatrics, University of California San Diego, La Jolla, California 92093-0672, saspector@ucsd.edu.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>the Rady Children's Hospital, San Diego, California 92123, and.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>UM1 AI068616</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 NS084912</GrantID>
<Acronym>NS</Acronym>
<Agency>NINDS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>UM1 AI106716</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>UM1 AI068632</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 NS104015</GrantID>
<Acronym>NS</Acronym>
<Agency>NINDS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>UM1 AI069536</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 CA172513</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R42 CA192656</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2018</Year>
<Month>02</Month>
<Day>23</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>J Biol Chem</MedlineTA>
<NlmUniqueID>2985121R</NlmUniqueID>
<ISSNLinking>0021-9258</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C561695">(+)-JQ1 compound</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D019380">Anti-HIV Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D001381">Azepines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C441289">BRD4 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D018797">Cell Cycle Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D007093">Imidazoles</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D009687">Nuclear Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000081082">Phosphoinositide-3 Kinase Inhibitors</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D047428">Protein Kinase Inhibitors</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011804">Quinolines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014157">Transcription Factors</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014230">Triazoles</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.137</RegistryNumber>
<NameOfSubstance UI="D058539">Phosphatidylinositol 3-Kinase</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>RUJ6Z9Y0DT</RegistryNumber>
<NameOfSubstance UI="C531198">dactolisib</NameOfSubstance>
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<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D019380" MajorTopicYN="N">Anti-HIV Agents</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001381" MajorTopicYN="N">Azepines</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018797" MajorTopicYN="N">Cell Cycle Proteins</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015658" MajorTopicYN="N">HIV Infections</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015497" MajorTopicYN="N">HIV-1</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007093" MajorTopicYN="N">Imidazoles</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008264" MajorTopicYN="N">Macrophages</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009687" MajorTopicYN="N">Nuclear Proteins</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058539" MajorTopicYN="N">Phosphatidylinositol 3-Kinase</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000081082" MajorTopicYN="N">Phosphoinositide-3 Kinase Inhibitors</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D047428" MajorTopicYN="N">Protein Kinase Inhibitors</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011804" MajorTopicYN="N">Quinolines</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014157" MajorTopicYN="N">Transcription Factors</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014230" MajorTopicYN="N">Triazoles</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014779" MajorTopicYN="N">Virus Replication</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">JQ1</Keyword>
<Keyword MajorTopicYN="Y">NVP-BEZ235</Keyword>
<Keyword MajorTopicYN="Y">SF2523</Keyword>
<Keyword MajorTopicYN="Y">autophagy</Keyword>
<Keyword MajorTopicYN="Y">autophagy-related protein 7 (ATG7)</Keyword>
<Keyword MajorTopicYN="Y">human immunodeficiency virus (HIV)</Keyword>
<Keyword MajorTopicYN="Y">macrophage</Keyword>
<Keyword MajorTopicYN="Y">phosphatidylinositol signaling</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year>
<Month>02</Month>
<Day>08</Day>
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<Month>02</Month>
<Day>21</Day>
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	Serveur d'exploration sur la rapamycine et les champignons
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Induction of autophagy by PI3K/MTOR and PI3K/MTOR/BRD4 inhibitors suppresses HIV-1 replication.

Induction of autophagy by PI3K/MTOR and PI3K/MTOR/BRD4 inhibitors suppresses HIV-1 replication.

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