Scholarlink

<p>Human immunodeficiency virus (HIV) persists in infected individuals despite effective antiretroviral therapy due to the rapid establishment of latent reservoirs, mainly composed of quiescent memory CD4+ T cells. The mechanisms governing latent reservoir formation remain poorly understood. Here, using single-cell RNA-seq and functional studies in human primary CD4+ T cell models, we show that HIV infection with reporter constructs and laboratory and patient-derived strains triggers transcriptomic remodelling, activating the p53 pathway and a quiescence programme mediated by Krüppel-like factor 2 (KLF2), a key quiescence regulator. Loss- and gain-of-function studies, including unbiased shRNA screens and confirmatory studies in CD4+ T cells from HIV+ donors, demonstrate that HIV infection drives KLF2 and p53 signalling, which downregulate MYC and proliferation pathways, resulting in proviral transcriptional silencing. This enhances latent reservoir formation in T cells, ensuring viral persistence. These findings present a mechanism for forming the latent HIV reservoir and broaden the repertoire of strategies through which viruses control host cells to their advantage.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

HIV infection reprogrammes CD4+ T cells for quiescence and entry into proviral latency

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月26日

查看全文
  • Leah M. Plasek Hegde,
  • Lalith S. Gunawardane,
  • Farshad Niazi,
  • Uri Mbonye,
  • Konstantin Leskov,
  • Gani Perez,
  • Curtis Dobrowolski,
  • Meenakshi Shukla,
  • William S. Nutt,
  • Jonathan Karn,
  • Saba Valadkhan

摘要

Human immunodeficiency virus (HIV) persists in infected individuals despite effective antiretroviral therapy due to the rapid establishment of latent reservoirs, mainly composed of quiescent memory CD4+ T cells. The mechanisms governing latent reservoir formation remain poorly understood. Here, using single-cell RNA-seq and functional studies in human primary CD4+ T cell models, we show that HIV infection with reporter constructs and laboratory and patient-derived strains triggers transcriptomic remodelling, activating the p53 pathway and a quiescence programme mediated by Krüppel-like factor 2 (KLF2), a key quiescence regulator. Loss- and gain-of-function studies, including unbiased shRNA screens and confirmatory studies in CD4+ T cells from HIV+ donors, demonstrate that HIV infection drives KLF2 and p53 signalling, which downregulate MYC and proliferation pathways, resulting in proviral transcriptional silencing. This enhances latent reservoir formation in T cells, ensuring viral persistence. These findings present a mechanism for forming the latent HIV reservoir and broaden the repertoire of strategies through which viruses control host cells to their advantage.