期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 12, 期 528, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aax6795
关键词
-
资金
- NIH [UM1 AI126603, UM1 AI126620, UM1 AI12661]
- Johns Hopkins Center for AIDS Research [P30AI094189]
- Howard Hughes Medical Institute
- Bill and Melinda Gates Foundation [OPP1115715]
- Bill and Melinda Gates Foundation [OPP1115715] Funding Source: Bill and Melinda Gates Foundation
The latent reservoir of HIV-1 in resting CD4(+) T cells is a major barrier to cure. It is unclear whether the latent reservoir resides principally in particular subsets of CD4(+) T cells, a finding that would have implications for understanding its stability and developing curative therapies. Recent work has shown that proliferation of HIV-1-infected CD4(+) T cells is a major factor in the generation and persistence of the latent reservoir and that latently infected T cells that have clonally expanded in vivo can proliferate in vitro without producing virions. In certain CD4(+) memory T cell subsets, the provirus may be in a deeper state of latency, allowing the cell to proliferate without producing viral proteins, thus permitting escape from immune clearance. To evaluate this possibility, we used a multiple stimulation viral outgrowth assay to culture resting naive, central memory (TCM), transitional memory (TTM), and effector memory (TEM) CD4(+) T cells from 10 HIV-1-infected individuals on antiretroviral therapy. On average, only 1.7% of intact proviruses across all T cell subsets were induced to transcribe viral genes and release replication-competent virus after stimulation of the cells. We found no consistent enrichment of intact or inducible proviruses in any T cell subset. Furthermore, we observed notable plasticity among the canonical memory T cell subsets after activation in vitro and saw substantial person-to-person variability in the inducibility of infectious virus release. This finding complicates the vision for a targeted approach for HIV-1 cure based on T cell memory subsets.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据