HETEROGENEITY OF LATENCY ESTABLISHMENT IN DIFFERENT HUMAN CD4+ T CELL SUBSETS STIMULATED WITH INTERLEUKIN-15
type: CreativeWork
description: The Human Immunodeficiency Virus (HIV) integrates its genome into the host DNA and persists for the lifetime of the infected cell. Even in the presence of an efficacious Highly Active Anti-Retroviral Therapy (HAART) treatment, a pool of latently infected cells persists and reactivates to produce viral particles if antiretroviral therapies are stopped or discontinued. This so-called latent reservoir is established mainly in CD4+ T memory ad naïve cells early during infection under conditions that are still not well defined. CD4+ T memory lymphocytes are highly heterogeneous and comprise both effector and long-lived subsets. This study aimed to analyze HIV latency establishment at the subset level in ex vivo primary CD4+ T cells stimulated with Interleukin-15 (IL-15) to mimic the pathophysiological conditions of the in vivo establishment during the early phases of infection. To do that, we used the dual-reporter virus HIV-GKO, which bears two different fluorescent reporters, one under the control of the HIV-LTR promoter and one under the control of a constitutive cellular promoter thus allowing the discrimination between transcriptionally silent infected cells and transcriptionally active infected cells. We demonstrated that HIV preferentially infects the more differentiated Central Memory (TCM), Transitional Memory (TTM) and Effector Memory (TEM) subsets. However, the less differentiated naïve and Stem-Cell Memory (TSCM) subsets were enriched in latency, suggesting that the rare infection of these compartments likely ends in a transcriptionally silent integrated provirus. This phenotype was independent of differential expression of the positive transcription elongation factor b (P-TEFb) components Cyclin T1 and phospho/Cyclin-dependent kinase 9 (P/CDK9). When we analyzed the cellular distribution of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor, which is important for HIV expression, we observed that nuclear levels …
abstract: The Human Immunodeficiency Virus (HIV) integrates its genome into the host DNA and persists for the lifetime of the infected cell. Even in the presence of an efficacious Highly Active Anti-Retroviral Therapy (HAART) treatment, a pool of latently infected cells persists and reactivates to produce viral particles if antiretroviral therapies are stopped or discontinued. This so-called latent reservoir is established mainly in CD4+ T memory ad naïve cells early during infection under conditions that are still not well defined. CD4+ T memory lymphocytes are highly heterogeneous and comprise both effector and long-lived subsets. This study aimed to analyze HIV latency establishment at the subset level in ex vivo primary CD4+ T cells stimulated with Interleukin-15 (IL-15) to mimic the pathophysiological conditions of the in vivo establishment during the early phases of infection. To do that, we used the dual-reporter virus HIV-GKO, which bears two different fluorescent reporters, one under the control of the HIV-LTR promoter and one under the control of a constitutive cellular promoter thus allowing the discrimination between transcriptionally silent infected cells and transcriptionally active infected cells. We demonstrated that HIV preferentially infects the more differentiated Central Memory (TCM), Transitional Memory (TTM) and Effector Memory (TEM) subsets. However, the less differentiated naïve and Stem-Cell Memory (TSCM) subsets were enriched in latency, suggesting that the rare infection of these compartments likely ends in a transcriptionally silent integrated provirus. This phenotype was independent of differential expression of the positive transcription elongation factor b (P-TEFb) components Cyclin T1 and phospho/Cyclin-dependent kinase 9 (P/CDK9). When we analyzed the cellular distribution of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor, which is important for HIV expression, we observed that nuclear levels …
author: BUTTA, GIACOMO MARIA
language: eng
keywords: HIV, latent reservoir, IL-15, CD4, memory subsets, Settore BIO/19 - Microbiologia Generale
date published: 2023-04-04
date modified: 2026-07-27T20:19:12Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/962049

PropertyValue
property ID: DOI
value: 10.13130/butta-giacomo-maria_phd2023-04-04