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AuthorCastro-Gonzalez, Sergiodc.contributor.author
AuthorShi, Yuhangdc.contributor.author
AuthorColomer-Lluch, Martadc.contributor.author
AuthorSong, Yingdc.contributor.author
AuthorMowery, Kaitlyndc.contributor.author
AuthorAlmodovar, Sharilyndc.contributor.author
AuthorBansal, Anjudc.contributor.author
AuthorKirchhoff, Frankdc.contributor.author
AuthorSparrer, Konstantindc.contributor.author
AuthorLiang, Chengyudc.contributor.author
AuthorSerra-Moreno, Ruthdc.contributor.author
Date of accession2020-06-26T13:07:47Zdc.date.accessioned
Available in OPARU since2020-06-26T13:07:47Zdc.date.available
Date of first publication2020-02-25dc.date.issued
AbstractMacroautophagy/autophagy is an auto-digestive pro-survival pathway activated in response to stress to target cargo for lysosomal degradation. In recent years, autophagy has become prominent as an innate antiviral defense mechanism through multiple processes, such as targeting virions and viral components for elimination. These exciting findings have encouraged studies on the ability of autophagy to restrict HIV. However, the role of autophagy in HIV infection remains unclear. Whereas some reports indicate that autophagy is detrimental for HIV, others have claimed that HIV deliberately activates this pathway to increase its infectivity. Moreover, these contrasting findings seem to depend on the cell type investigated. Here, we show that autophagy poses a hurdle for HIV replication, significantly reducing virion production. However, HIV-1 uses its accessory protein Nef to counteract this restriction. Previous studies have indicated that Nef affects autophagy maturation by preventing the fusion between autophagosomes and lysosomes. Here, we uncover that Nef additionally blocks autophagy initiation by enhancing the association between BECN1 and its inhibitor BCL2, and this activity depends on the cellular E3 ligase PRKN. Remarkably, the ability of Nef to counteract the autophagy block is more frequently observed in pandemic HIV-1 and its simian precursor SIVcpz infecting chimpanzees than inHIV-2 and its precursor SIVsmm infecting sooty mangabeys. In summary, our findings demonstrate that HIV-1 is susceptible to autophagy restriction and define Nef as the primary autophagy antagonist of this antiviral process.dc.description.abstract
Languageen_USdc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseCC BY-NC-ND 4.0dc.rights
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHAutophagydc.subject.mesh
MeSHImmunity, Innatedc.subject.mesh
MeSHHIVdc.subject.mesh
TitleHIV-1 Nef counteracts autophagy restriction by enhancing the association between BECN1 and its inhibitor BCL2 in a PRKN-dependent mannerdc.title
Resource typeWissenschaftlicher Artikeldc.type
VersionpublishedVersiondc.description.version
DOIhttp://dx.doi.org/10.18725/OPARU-32198dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-32260-0dc.identifier.urn
GNDAutophagie <Physiologie>dc.subject.gnd
GNDAngeborene Immunitätdc.subject.gnd
GNDHIVdc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
InstitutionUKU. Institut für Molekulare Virologieuulm.affiliationSpecific
Peer reviewjauulm.peerReview
DCMI TypeTextuulm.typeDCMI
CategoryPublikationenuulm.category
In cooperation withTexas Tech Universityuulm.cooperation
In cooperation withGermans Trias i Pujol Research Instituteuulm.cooperation
In cooperation withUniversity of Southern Californiauulm.cooperation
In cooperation withUniversity of Alabama at Birminghamuulm.cooperation
Is Supplemented Byhttps://figshare.com/articles/HIV-1_Nef_counteracts_autophagy_restriction_by_enhancing_the_association_between_BECN1_and_its_inhibitor_BCL2_in_a_PRKN-dependent_manner/11898666uulm.relation.isSupplementedBy
DOI of original publication10.1080/15548627.2020.1725401dc.relation1.doi
Source - Title of sourceAutophagysource.title
Source - Place of publicationTaylor and Francissource.publisher
Source - Volume2020source.volume
Source - Year2020source.year
Source - ISSN1554-8627source.identifier.issn
Source - eISSN1554-8635source.identifier.eissn
EU projectVIAR / Virus-induced autophagy restriction / EC / H2020 / 794803uulm.projectEU
FundingDFG [SP1600/4-1]uulm.funding
FundingSFB 1279 / Nutzung des menschlichen Peptidoms für die Entwicklung neuer antimikrobieller und anti-Krebs Therapeutika / DFGuulm.funding
FundingSPP 1923 / Innate Sensing and Restriction of Retroviruses / DFGuulm.funding
University Bibliographyjauulm.unibibliographie


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