Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones.
Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones.
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DOI：
10.1016/j.immuni.2022.03.004
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发表时间：
2022-06-14
期刊：
影响因子：
32.4
通讯作者：
Ho, Ya-Chi
中科院分区：
文献类型：
--
作者：
Collora, Jack A.;Liu, Runxia;Pinto-Santini, Delia;Ravindra, Neal;Ganoza, Carmela;Lama, Javier R.;Alfaro, Ricardo;Chiarella, Jennifer;Spudich, Serena;Mounzer, Karam;Tebas, Pablo;Montaner, Luis J.;van Dijk, David;Duerr, Ann;Ho, Ya-Chi
Understanding the drivers and markers of clonally expanding HIV-1-infected CD4+ T cells is essential for HIV-1 eradication. We used single-cell ECCITE-seq, which captures surface protein expression, cellular transcriptome, HIV-1 RNA, and TCR sequences within the same single cell to track clonal expansion dynamics in longitudinally archived samples from six HIV-1-infected individuals (during viremia and after suppressive antiretroviral therapy) and two uninfected individuals, in unstimulated conditions and after CMV and HIV-1 antigen stimulation. Despite antiretroviral therapy, persistent antigen and TNF responses shaped T cell clonal expansion. HIV-1 resided in Th1 polarized, antigen-responding T cells expressing BCL2 and SERPINB9 that may resist cell death. HIV-1 RNA+ T cell clones were larger in clone size, established during viremia, persistent after viral suppression, and enriched in GZMB+ cytotoxic effector memory Th1 cells. Targeting HIV-1-infected cytotoxic CD4+ T cells and drivers of clonal expansion provides another direction for HIV-1 eradication. Using single-cell ECCITE-seq, Collora et al. profiled 267 HIV-1 RNA+ cells and 68 expanded HIV-1 RNA+ T cell clones from 215,458 CD4+ T cells. HIV-1 resides in GZMB+ cytotoxic Th1 effector memory CD4+ T cell clones that are large and persistent. HIV-1-infected cytotoxic CD4+ T cells may evade cytotoxic CD8+ T cell killing through Seprin B9 degradation of granzyme B.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
6.7
作者：
Fromentin R;Bakeman W;Lawani MB;Khoury G;Hartogensis W;DaFonseca S;Killian M;Epling L;Hoh R;Sinclair E;Hecht FM;Bacchetti P;Deeks SG;Lewin SR;Sékaly RP;Chomont N
通讯作者：
Chomont N
DOI：
10.1073/pnas.94.24.13193
发表时间：
1997-11-25
影响因子：
11.1
作者：
Chun, TW;Stuyver, L;Fauci, AS
通讯作者：
Fauci, AS
影响因子：
8
作者：
Coffin, John M.;Wells, David W.;Hughes, Stephen H.
通讯作者：
Hughes, Stephen H.
影响因子：
6.4
作者：
Crooks, Amanda M.;Bateson, Rosalie;Archin, Nancie M.
通讯作者：
Archin, Nancie M.