000127126 001__ 127126
000127126 005__ 20240228140907.0
000127126 0247_ $$2doi$$a10.1128/JVI.00787-15
000127126 0247_ $$2pmid$$apmid:26018155
000127126 0247_ $$2pmc$$apmc:PMC4505648
000127126 0247_ $$2ISSN$$a0022-538X
000127126 0247_ $$2ISSN$$a1098-5514
000127126 0247_ $$2altmetric$$aaltmetric:4070153
000127126 037__ $$aDKFZ-2017-03152
000127126 041__ $$aeng
000127126 082__ $$a570
000127126 1001_ $$aMetz, Philippe$$b0
000127126 245__ $$aDengue Virus Inhibition of Autophagic Flux and Dependency of Viral Replication on Proteasomal Degradation of the Autophagy Receptor p62.
000127126 260__ $$aBaltimore, Md.$$bSoc.$$c2015
000127126 3367_ $$2DRIVER$$aarticle
000127126 3367_ $$2DataCite$$aOutput Types/Journal article
000127126 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1525418675_19749
000127126 3367_ $$2BibTeX$$aARTICLE
000127126 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000127126 3367_ $$00$$2EndNote$$aJournal Article
000127126 520__ $$aAutophagic flux involves formation of autophagosomes and their degradation by lysosomes. Autophagy can either promote or restrict viral replication. In the case of Dengue virus (DENV), several studies report that autophagy supports the viral replication cycle, and describe an increase of autophagic vesicles (AVs) following infection. However, it is unknown how autophagic flux is altered to result in increased AVs. To address this question and gain insight into the role of autophagy during DENV infection, we established an unbiased, image-based flow cytometry approach to quantify autophagic flux under normal growth conditions and in response to activation by nutrient deprivation or them TOR inhibitor Torin1.We found that DENV induced an initial activation of autophagic flux, followed by inhibition of general and specific autophagy. Early after infection, basal and activated autophagic flux was enhanced. However, during established replication, basal and Torin1-activated autophagic flux was blocked, while autophagic flux activated by nutrient deprivation was reduced, indicating a block to AV formation and reduced AV degradation capacity. During late infection AV levels increased as a result of inefficient fusion of autophagosomes with lysosomes. In addition, endolysosomal trafficking was suppressed, while lysosomal activities were increased.We further determined that DENV infection progressively reduced levels of the autophagy receptor SQSTM1/p62 via proteasomal degradation. Importantly, stable overexpression of p62 significantly suppressed DENV replication, suggesting a novel role for p62 as a viral restriction factor. Overall, our findings indicate that in the course of DENV infection, autophagy shifts from a supporting to an antiviral role, which is countered by DENV.Autophagic flux is a dynamic process starting with the formation of autophagosomes and ending with their degradation after fusion with lysosomes. Autophagy impacts the replication cycle of many viruses. However, thus far the dynamics of autophagy in case of Dengue virus (DENV) infections has not been systematically quantified. Therefore, we used high-content, imaging-based flow cytometry to quantify autophagic flux and endolysosomal trafficking in response to DENV infection. We report that DENV induced an initial activation of autophagic flux, followed by inhibition of general and specific autophagy. Further, lysosomal activity was increased, but endolysosomal trafficking was suppressed confirming the block of autophagic flux. Importantly, we provide evidence that p62, an autophagy receptor, restrict DENV replication and was specifically depleted in DENV-infected cells via increased proteasomal degradation. These results suggest that during DENV infection autophagy shifts from a proviral to an antiviral cellular process, which is counteracted by the virus.
000127126 536__ $$0G:(DE-HGF)POF3-316$$a316 - Infections and cancer (POF3-316)$$cPOF3-316$$fPOF III$$x0
000127126 588__ $$aDataset connected to CrossRef, PubMed,
000127126 650_7 $$2NLM Chemicals$$aAdaptor Proteins, Signal Transducing
000127126 650_7 $$2NLM Chemicals$$aSQSTM1 protein, human
000127126 650_7 $$2NLM Chemicals$$aSequestosome-1 Protein
000127126 7001_ $$aChiramel, Abhilash$$b1
000127126 7001_ $$aChatel-Chaix, Laurent$$b2
000127126 7001_ $$aAlvisi, Gualtiero$$b3
000127126 7001_ $$aBankhead, Peter$$b4
000127126 7001_ $$0P:(DE-HGF)0$$aMora-Rodriguez, Rodrigo$$b5
000127126 7001_ $$aLong, Gang$$b6
000127126 7001_ $$0P:(DE-He78)a8657988a6082d4d90605e15cd5d3302$$aHamacher-Brady, Anne$$b7$$udkfz
000127126 7001_ $$0P:(DE-He78)5bf984e94f0a31773a103cd293e01f92$$aBrady, Nathan R$$b8$$udkfz
000127126 7001_ $$0P:(DE-He78)1d3968d2f0ff3eae55f6b2ea4c474387$$aBartenschlager, Ralf$$b9$$eLast author$$udkfz
000127126 773__ $$0PERI:(DE-600)1495529-5$$a10.1128/JVI.00787-15$$gVol. 89, no. 15, p. 8026 - 8041$$n15$$p8026 - 8041$$tJournal of virology$$v89$$x1098-5514$$y2015
000127126 909CO $$ooai:inrepo02.dkfz.de:127126$$pVDB
000127126 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ
000127126 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a8657988a6082d4d90605e15cd5d3302$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ
000127126 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)5bf984e94f0a31773a103cd293e01f92$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000127126 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)1d3968d2f0ff3eae55f6b2ea4c474387$$aDeutsches Krebsforschungszentrum$$b9$$kDKFZ
000127126 9131_ $$0G:(DE-HGF)POF3-316$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vInfections and cancer$$x0
000127126 9141_ $$y2015
000127126 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ VIROL : 2015
000127126 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000127126 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000127126 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000127126 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000127126 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000127126 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bThomson Reuters Master Journal List
000127126 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000127126 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000127126 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000127126 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000127126 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000127126 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000127126 9201_ $$0I:(DE-He78)B190-20160331$$kB190$$le:Bio Nachwuchsgruppe Lysosomale Systembiologie$$x0
000127126 9201_ $$0I:(DE-He78)F170-20160331$$kF170$$lVirus-assoziierte Karzinogenese$$x1
000127126 980__ $$ajournal
000127126 980__ $$aVDB
000127126 980__ $$aI:(DE-He78)B190-20160331
000127126 980__ $$aI:(DE-He78)F170-20160331
000127126 980__ $$aUNRESTRICTED