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2021-02-09Zeitschriftenartikel DOI: 10.1186/s12977-021-00548-2
Vpx enhances innate immune responses independently of SAMHD1 during HIV-1 infection
dc.contributor.authorCingöz, Oya
dc.contributor.authorArnow, Nicolas D.
dc.contributor.authorTorrents, Mireia Puig
dc.contributor.authorBannert, Norbert
dc.date.accessioned2021-02-25T09:08:16Z
dc.date.available2021-02-25T09:08:16Z
dc.date.issued2021-02-09none
dc.identifier.other10.1186/s12977-021-00548-2
dc.identifier.urihttp://edoc.rki.de/176904/7837
dc.description.abstractBackground The genomes of HIV-2 and some SIV strains contain the accessory gene vpx, which carries out several functions during infection, including the downregulation of SAMHD1. Vpx is also commonly used in experiments to increase HIV-1 infection efficiency in myeloid cells, particularly in studies that investigate the activation of antiviral pathways. However, the potential effects of Vpx on cellular innate immune signaling is not completely understood. We investigated whether and how Vpx affects ISG responses in monocytic cell lines and MDMs during HIV-1 infection. Results HIV-1 infection at excessively high virus doses can induce ISG activation, although at the expense of high levels of cell death. At equal infection levels, the ISG response is potentiated by the presence of Vpx and requires the initiation of reverse transcription. The interaction of Vpx with the DCAF1 adaptor protein is important for the enhanced response, implicating Vpx-mediated degradation of a host factor. Cells lacking SAMHD1 show similarly augmented responses, suggesting an effect that is independent of SAMHD1 degradation. Overcoming SAMHD1 restriction in MDMs to reach equal infection levels with viruses containing and lacking Vpx reveals a novel function of Vpx in elevating innate immune responses. Conclusions Vpx likely has as yet undefined roles in infected cells. Our results demonstrate that Vpx enhances ISG responses in myeloid cell lines and primary cells independently of its ability to degrade SAMHD1. These findings have implications for innate immunity studies in myeloid cells that use Vpx delivery with HIV-1 infection.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subjectInfectioneng
dc.subjectInnate immunityeng
dc.subjectInterferoneng
dc.subjectMDMeng
dc.subjectMacrophageeng
dc.subjectTHP-1eng
dc.subjectISGeng
dc.subjectISREeng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleVpx enhances innate immune responses independently of SAMHD1 during HIV-1 infectionnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:0257-176904/7837-6
dc.identifier.doihttps://doi.org/10.1186/s12977-021-00548-2
dc.identifier.doihttp://dx.doi.org/10.25646/8068
dc.type.versionpublishedVersionnone
local.edoc.container-titleRetrovirologynone
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://retrovirology.biomedcentral.com/articles/10.1186/s12977-021-00548-2none
local.edoc.container-publisher-nameBMCnone
local.edoc.container-volume18none
local.edoc.container-issue4none
local.edoc.container-reportyear2021none
local.edoc.container-firstpage1none
local.edoc.container-lastpage15none
local.edoc.rki-departmentInfektionskrankheitennone
dc.description.versionPeer Reviewednone

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