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Ndhlovu, Zaza

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Ndhlovu

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Zaza

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Ndhlovu, Zaza

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2012 - 20202

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Author's Publications: search.filters.isAuthorOfPublication.995c3201-3939-4fe7-ac40-5625309ac4cc

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    A High-Dimensional Immune Monitoring Model of HIV-1-Specific CD8 T Cell Responses Accurately Identifies Subjects Achieving Spontaneous Viral Control
    (BioMed Central, 2012) Proudfoot, J; Vine, S; Cesa, K; Piechocka-Trocha, A; Ndhlovu, Zaza; Chibnik, Lori; McMullen, A; Porichis, Filippos; Alvino, Donna Marie; De Jager, Philip; Walker, Bruce; Kaufmann, Daniel E.
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    Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection
    (Cold Spring Harbor Laboratory, 2020-03-23) Kazer, Samuel W.; Aicher, Toby P.; Muema, Daniel M.; Carroll, Shaina L.; Ordovas-Montanes, Jose; Maio, Vincent M.; Tu, Andy A.; Ziegler, Carly G.K.; Nyquist, Sarah K.; Wong, Emily; Ismail, Nasreen; Dong, Mary; Moodley, Amber; Berger Leighton, Bonnie; Love, J. Christopher; Dong, Krista L.; Leslie, Alasdair; Ndhlovu, Zaza; Ndung'u, Thumbi; Walker, Bruce; Shalek, Alexander
    Cellular immunity is critical for controlling intracellular pathogens, but the dynamics and cooperativity of the evolving host response to infection are not well defined. Here, we apply single-cell RNA-sequencing to longitudinally profile pre- and immediately post-HIV infection peripheral immune responses of multiple cell types in four untreated individuals. Onset of viremia induces a strong transcriptional interferon response integrated across most cell types, with subsequent pro-inflammatory T cell differentiation, monocyte MHC-II upregulation, and cytolytic killing. With longitudinal sampling, we nominate key intra- and extracellular drivers that induce these programs, and assign their multi-cellular targets, temporal ordering, and duration in acute infection. Two individuals studied developed spontaneous viral control, associated with initial elevated frequencies of proliferating cytotoxic cells, inclusive of a previously unappreciated proliferating natural killer (NK) cell subset. Our study presents a unified framework for characterizing immune evolution during a persistent human viral infection at single-cell resolution, and highlights programs that may drive response coordination and influence clinical trajectory.