Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection

Biology Biology
Genomics Genomics
Immunology Immunology
Infectious Disease Infectious Disease
Alex K. Shalek Alex K. Shalek
Carly Ziegler Carly Ziegler
José Ordovas-Montañes José Ordovas-Montañes
Sam Kazer Sam Kazer
Sarah Nyquist Sarah Nyquist
Shaina Carroll Shaina Carroll
Toby Aicher Toby Aicher

Kazer S.W. et al.▾ Kazer S.W., Aicher T.P., Muema D.M., Carroll S.L., Ordovas-Montanes O., Ziegler C.G.K., Nyquist S.K., Wong E.B. Ismail N., Dong M., Moodley A., Dong K.L., Ndhlovu Z.M., Ndung'u T., Walker B.D., Shalek A.K.


May, 2019


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.