Phenotypic analysis of the unstimulated in vivo HIV CD4 T cell reservoir
Neidleman, Jason et al. (2020), Phenotypic analysis of the unstimulated in vivo HIV CD4 T cell reservoir , Dryad, Dataset, https://doi.org/10.7272/Q6KK991S
The latent reservoir is a main barrier for curing HIV. But because latently-infected cells cannot be phenotyped directly, the features of the in vivo reservoir have remained elusive. Here, we describe a method that leverages high-dimensional phenotyping using CyTOF to trace latently-infected cells reactivated ex vivo to their original pre-activation states. Our results suggest that contrary to common assumptions, the reservoir is not randomly distributed among cell subsets, and is remarkably conserved between individuals. However, reservoir composition differs between tissues and blood, as do cells successfully reactivated by different latency reversing agents. By selecting 8-10 of our 39 original CyTOF markers, we were able to isolate highly purified populations of unstimulated in vivo latent cells. These purified populations were highly enriched for replication-competent and intact provirus, transcribed HIV, and displayed clonal expansion. The ability to isolate unstimulated latent cells from infected individuals enables previously impossible studies of HIV persistence.
Included are the raw CSV files for the atlas CD4+ T cells ("atlas") and kNN latent cells ("kNN") for specimens in the study analyzed by PP-SLIDE. Each row corresponds to a cell, and each column indicates the arcsinh-transformed values for each measured protein parameter. Zero values correspond to instances where the corresponding metal-conjugated antibody was not detected by the CyTOF instrument.