Browsing by Author "Bosinger, Steven E"

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    Delineation and Modulation of the Natural Killer Cell Transcriptome in Rhesus Macaques During ZIKV and SIV Infections.
    (Frontiers in cellular and infection microbiology, 2020-01) Aid, Malika; Ram, Daniel R; Bosinger, Steven E; Barouch, Dan H; Reeves, R Keith
    Natural killer (NK) cells are crucial regulators of antiviral and anti-tumor immune responses. Although in humans some NK cell transcriptional programs are relatively well-established, NK cell transcriptional networks in non-human primates (NHP) remain poorly delineated. Here we performed RNA-Seq experiments using purified NK cells from experimentally naïve rhesus macaques, providing the first transcriptional characterization of pure NK cells in any NHP species. This novel NK cell transcriptomic signature (NK RMtsig) overlaps with published human NK signatures, allowing us to identify new key signaling and transcription factor networks underlying NK cell function. Finally, we show that applying NK RMtsig to an unrelated rhesus macaque cohort infected with SIVmac251 or ZIKV can sensitively detect NK cell repertoire perturbations, thus confirming applicability of this approach. In sum, we propose this NHP NK cell signature will serve as a useful resource for future studies involving infection, disease or treatment modalities in NHP.
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    Species-specific host factors rather than virus-intrinsic virulence determine primate lentiviral pathogenicity.
    (Nature communications, 2018-04) Joas, Simone; Parrish, Erica H; Gnanadurai, Clement W; Lump, Edina; Stürzel, Christina M; Parrish, Nicholas F; Learn, Gerald H; Sauermann, Ulrike; Neumann, Berit; Rensing, Kerstin Mätz; Fuchs, Dietmar; Billingsley, James M; Bosinger, Steven E; Silvestri, Guido; Apetrei, Cristian; Huot, Nicolas; Garcia-Tellez, Thalia; Müller-Trutwin, Michaela; Hotter, Dominik; Sauter, Daniel; Stahl-Hennig, Christiane; Hahn, Beatrice H; Kirchhoff, Frank
    HIV-1 causes chronic inflammation and AIDS in humans, whereas related simian immunodeficiency viruses (SIVs) replicate efficiently in their natural hosts without causing disease. It is currently unknown to what extent virus-specific properties are responsible for these different clinical outcomes. Here, we incorporate two putative HIV-1 virulence determinants, i.e., a Vpu protein that antagonizes tetherin and blocks NF-κB activation and a Nef protein that fails to suppress T cell activation via downmodulation of CD3, into a non-pathogenic SIVagm strain and test their impact on viral replication and pathogenicity in African green monkeys. Despite sustained high-level viremia over more than 4 years, moderately increased immune activation and transcriptional signatures of inflammation, the HIV-1-like SIVagm does not cause immunodeficiency or any other disease. These data indicate that species-specific host factors rather than intrinsic viral virulence factors determine the pathogenicity of primate lentiviruses.
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    The IDO inhibitor 1-methyl tryptophan activates the aryl hydrocarbon receptor response in mesenchymal stromal cells
    (Oncotarget, 2017-11-03) Lewis, Holly C; Chinnadurai, Raghavan; Bosinger, Steven E; Galipeau, Jacques