Kazer, Samuel W.Aicher, Toby P.Muema, Daniel M.Carroll, Shaina L.Ordovas-Montanes, JoseMaio, Vincent M.Tu, Andy A.Ziegler, Carly G.K.Nyquist, Sarah K.Wong, EmilyIsmail, NasreenDong, MaryMoodley, AmberBerger Leighton, BonnieLove, J. ChristopherDong, Krista L.Leslie, AlasdairNdhlovu, ZazaNdung'u, ThumbiWalker, BruceShalek, Alexander2022-08-292020-03-23Kazer, Samuel W., Toby P. Aicher, Daniel M. Muema, Shaina L. Carroll, Jose Ordovas-Montanes, Vincent M. Maio, Andy A. Tu et al. "Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection." Nature Medicine 26, no. 4 (2020): 511-518. DOI: 10.1101/654814https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37373105Cellular 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.en-USJournal Article2022-08-2910.1101/654814