GEO series
Single cell transcriptomic analysis of acute and early ART-treated HIV-1-infected CD4+T cells from a reservoir-marking humanized mouse model
GSE236107
Homo sapiens; Mus musculus
Expression profiling by high throughput sequencing
14 samples
Submitted 2024/12/31
Platform GPL25526Platform GPL24676
Summary
Human immunodeficiency virus (HIV-1) infects and depletes CD4+ T helper cells and can persist within these cells in a latent state during treatment with effective antiretroviral therapy (ART). A latent viral reservoir represents a major barrier to a cure for HIV-1 infection. A longstanding obstacle to understanding the reservoir has been the inability to identify and characterize latent cells without activating them and disrupting their resting state. To address this challenge, we have developed an HIV-1-induced lineage tracing (HILT) humanized mouse model that irreversibly marks HIV-infected cells. The system employs a genetically encoded Cre-lox switch transduced into hematopoietic stem cells which are transplanted into immunodeficient mice. Infection of CD4+ T cells in HILT mice with a Cre-expressing HIV clone irreversibly marks infected cells by switching dsRedExpress2 to EGFP expression, a phenotype that is maintained in cell harboring proviruses that are transcriptionally silent during ART. Single cell RNA sequencing (scRNAseq) of infected T cells in the presence or absence of ART reveals HIV infection in diverse CD4+ T cell transcriptional lineages indicating that infected cells with active or suppressed transcription exist in many different T cell lineages. We examined genetic pathways that are more frequently altered in infected cells when compared with uninfected bystander cells. A comparison of pathways that are regulated in opposite directions in acute versus early ART-treated (persistent) infection identified EIF2α-, sirtuin-, and ILK-signaling pathways which contain known transcriptional regulators of HIV transcription. Lastly, we find that resveratrol, a drug that impact sirtuin pathways can influence latency establishment in an acute infection setting.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE236107_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 14 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA989047 and SRA study SRP446498. Searching any of these in the dataset finder brings you back here.
Study design
13 conditions, each sampled once — no replicated groups
Mouse_A3_dsRed ×2
Read from 14 sample titles: 13 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM7518379 Mouse_A1_Mixed
- GSM7518380 Mouse_A2_dsRed
- GSM7518381 Mouse_A2_GFP
- GSM7518382 Mouse_A3_dsRed1
- GSM7518383 Mouse_A3_dsRed2
- GSM7518384 Mouse_A3_GFP
- GSM7518385 Mouse_T1_dsRed
- GSM7518386 Mouse_T1_GFP
- GSM7518387 Mouse_T2_GFP
- GSM7518388 Mouse_T3_Mixed
- GSM7518389 Mouse_U1_dsRed
- GSM7518390 Mouse_U1_Unmarked
- GSM7518391 Mouse_U2_dsRed
- GSM7518392 Mouse_U2_Unmarked
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