KAP1: a new repressor factor for HIV-1 gene transcription
- Supervisor: Carine Van Lint
- Research center: Virologie moléculaire
- Research start date: 01.10.2019
According to the UNAIDS organization, since 1990, around 38 million of people passed away due to the human immunodeficiency virus 1 (HIV-1) pandemic. Despite the existence of an effective and life-prolonging combinatory antiretroviral therapy (cART), eradication of the HIV-1 infection is still a worldwide challenge for Health authorities. HIV+ cART-treated patients maintain a residual low-level viremia, because the virus persists in partly under the form of cellular reservoirs of latently-infected cells, which seriously challenge the hope for HIV-1 eradication. These cellular viral reservoirs, insensitive to cART, are from different origins and are found in many sites, including circulating cells, the lymphoid system, the gut associated lymphoid tissues, the brain and other tissues. They contain transcriptionally-repressed HIV-1 proviruses and escape the host immune system. These latently-infected cells could be responsible for the rapid rebound of plasma viral load observed after cART interruption in patients. Therefore, it is crucial to understand the multiple molecular factors involved in HIV-1 latency, a highly dynamical and multifactorial phenomenon involving numerous interconnected processes, notably at the epigenetic and transcriptional levels. The objective of this project is to understand how the transcriptional repressor KAP1 regulate HIV-1 transcription and latency. Altogether this project will provide the identification of new pathways, and therefore new therapeutic targets, involved in the establishment, persistence of latency and epigenetic reactivation of HIV-1 reservoirs, that are necessary for the development of new drugs for HIV-1 functional cure.