Importance of cellular factors LSD1 and HIC-1 on HIV-1 restriction expression in microglial cells
type: Dataset
description: Even though current multitherapies maintain HIV infection under control, they unfortunately do not achieve viral eradication due to the existence of latently infected cell reservoirs. Microglial cells are resident macrophages and the main HIV-1 target in brain. They have been described as a long-lived HIV-1 cell reservoir, and so appear as a one of the main obstacle to viral clearance. Thus, understanding of the mechanisms implicated in the establishment and maintaining of viral latency in these cells is a critical step on the way towards an HIV cure. Our team already demonstrated the implication of the cellular transcription factor CTIP2 in the establishment of HIV-1 silencing. In this work, I present two other cellular factors, LSD1 and HIC1 as new HIV-1 transcriptionnal expression inhibitors in microglial cells. LSD1 cooperates with CTIP2 to promote the establishment of epigenetic marks associated to heterochromatin structure at the viral promoter. LSD1 act as an anchoring plateform for CTIP2, and so the CTIP2-associated mutli-enzymatic chromatin remodeling complex, but also recruits the COMPASS methyltransferase complex. Unlike CTIP2 and LSD1, the tumor suppressor HIC1 disrupts the TAT-mediated transactivation cycle. HIC1 is beforehand modified post-translationnaly by the deacetylase SIRT1 and then counteracts TAT activity in order to limit viral transcription reactivation. Thus, while CTIP2 and LSD1 favour latency establishment, HIC1 maintains provirus silencing in microglial cells. All together, the results presented in this work introduce two new viral expression restriction factors and new potential therapeutic targets in reservoir purge strategies.
identifier: NNT: 2012STRAJ081
issued: 2026-05-11T12:11:45.643166
language: fr
modified: 2026-05-11T12:11:45.643172
contact point: Organization
  fn: CCSD
keyword: chromatin
keyword: chromatine
keyword: ctip2
keyword: hic1
keyword: hiv-1
keyword: infoeu-reposemanticsdoctoralthesis
keyword: latence
keyword: latency
keyword: lsd-1
keyword: lsd1
keyword: microgliale-cells
keyword: microglie
keyword: reservoirs
keyword: sdvbbmlife-sciences-q-biobiochemistry-molecular-biology
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: sirt1
keyword: tat
keyword: theses
keyword: vih-1
landing page: https://theses.hal.science/tel-00813219

Importance of cellular factors LSD1 and HIC-1 on HIV-1 restriction expression in microglial cells
type: Distribution
format: HTML
issued: 2026-05-11T12:11:45.695328
modified: 2026-05-11T12:11:45.607312
access URL: https://theses.hal.science/tel-00813219

test_moissonnage_selune
type: Agent