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dc.contributor.authorElsner, Carina
dc.contributor.authorPonnurangam, Aparna
dc.contributor.authorKazmierski, Julia
dc.contributor.authorZillinger, Thomas
dc.contributor.authorJansen, Jenny
dc.contributor.authorTodt, Daniel
dc.contributor.authorDöhner, Katinka
dc.contributor.authorXu, Shuting
dc.contributor.authorDucroux, Aurélie
dc.contributor.authorKriedemann, Nils
dc.contributor.authorMalassa, Angelina
dc.contributor.authorLarsen, Pia-Katharina
dc.contributor.authorHartmann, Gunther
dc.contributor.authorBarchet, Winfried
dc.contributor.authorSteinmann, Eike
dc.contributor.authorKalinke, Ulrich
dc.contributor.authorSodeik, Beate
dc.contributor.authorGoffinet, Christine
dc.date.accessioned2022-08-10T10:10:32Z
dc.date.available2022-08-10T10:10:32Z
dc.date.issued2020-07-24
dc.identifier.pmid32709741
dc.identifier.doi10.1073/pnas.2002481117
dc.identifier.urihttp://hdl.handle.net/10033/623245
dc.description.abstractThe DNA sensor cGAS catalyzes the production of the cyclic dinucleotide cGAMP, resulting in type I interferon responses. We addressed the functionality of cGAS-mediated DNA sensing in human and murine T cells. Activated primary CD4+ T cells expressed cGAS and responded to plasmid DNA by upregulation of ISGs and release of bioactive interferon. In mouse T cells, cGAS KO ablated sensing of plasmid DNA, and TREX1 KO enabled cells to sense short immunostimulatory DNA. Expression of IFIT1 and MX2 was downregulated and upregulated in cGAS KO and TREX1 KO T cell lines, respectively, compared to parental cells. Despite their intact cGAS sensing pathway, human CD4+ T cells failed to mount a reverse transcriptase (RT) inhibitor-sensitive immune response following HIV-1 infection. In contrast, infection of human T cells with HSV-1 that is functionally deficient for the cGAS antagonist pUL41 (HSV-1ΔUL41N) resulted in a cGAS-dependent type I interferon response. In accordance with our results in primary CD4+ T cells, plasmid challenge or HSV-1ΔUL41N inoculation of T cell lines provoked an entirely cGAS-dependent type I interferon response, including IRF3 phosphorylation and expression of ISGs. In contrast, no RT-dependent interferon response was detected following transduction of T cell lines with VSV-G-pseudotyped lentiviral or gammaretroviral particles. Together, T cells are capable to raise a cGAS-dependent cell-intrinsic response to both plasmid DNA challenge or inoculation with HSV-1ΔUL41N. However, HIV-1 infection does not appear to trigger cGAS-mediated sensing of viral DNA in T cells, possibly by revealing viral DNA of insufficient quantity, length, and/or accessibility to cGAS.en_US
dc.language.isoenen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectHIV-1en_US
dc.subjectHSV-1en_US
dc.subjectT cellsen_US
dc.subjectcGASen_US
dc.subjectinnate sensingen_US
dc.titleAbsence of cGAS-mediated type I IFN responses in HIV-1-infected T cells.en_US
dc.typeArticleen_US
dc.identifier.eissn1091-6490
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.source.volume117
dc.source.issue32
dc.source.beginpage19475
dc.source.endpage19486
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.countryUnited States


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International