This Cell/Nature Medicine study from the Shalek Lab presents a longitudinal, single-cell RNA sequencing analysis of immune responses during hyperacute HIV-1 infection, profiling more than 59,000 immune cells from individuals tracked before and through early infection. By combining experimental and computational approaches, the team identifies dynamic gene expression programs that vary across both time and cell type, revealing coordinated, multicellular immune behaviors that are obscured in bulk analyses. The work uncovers an early, system-wide interferon response followed by temporally aligned programs including proinflammatory T cell differentiation, sustained monocyte activation, and persistent natural killer cell cytotoxicity. Importantly, the study highlights transient cellular states—such as proliferating NK cells—that may correlate with improved viral control, establishing a framework for dissecting complex immune dynamics and informing future HIV therapeutic and vaccine strategies.
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