Louise Leyre
A5065911011- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- HIV/AIDS Research and Interventions
- Immune responses and vaccinations
- HIV/AIDS drug development and treatment
- SARS-CoV-2 and COVID-19 Research
- HIV-related health complications and treatments
- Immunodeficiency and Autoimmune Disorders
- HIV, TB, and STIs Epidemiology
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- COVID-19 Clinical Research Studies
- Pharmacological Effects of Natural Compounds
- Hepatitis C virus research
- Systemic Lupus Erythematosus Research
- Syphilis Diagnosis and Treatment
- HIV, Drug Use, Sexual Risk
- Phagocytosis and Immune Regulation
- Herpesvirus Infections and Treatments
- COVID-19 Impact on Reproduction
Cornell University
2020-2025
Weill Cornell Medicine
2020-2024
Icahn School of Medicine at Mount Sinai
2020-2024
Centre Hospitalier de l’Université de Montréal
2017-2023
Université de Montréal
2018-2019
The phenotypic characterization of the cells in which HIV persists during antiretroviral therapy (ART) remains technically challenging. We developed a simple flow cytometry-based assay to quantify and characterize infected producing proteins untreated treated infection. By combining two antibodies targeting capsid standard intracellular staining protocol, we demonstrate that p24-producing can be detected with high specificity sensitivity blood from people living HIV. In individuals,...
Although a large pool of cells is infected during acute HIV infection, most these early targets are rapidly cleared upon ART initiation.
Before initiation of antiretroviral therapy (ART), HIV-specific CD8+ T cells are dysfunctional and short lived. To better understand the relationship between HIV reservoir in CD4+ magnitude differentiation status cells, we investigated these from acute chronic HIV-infected individuals after 2 years ART. Although both cell responses declined significantly ART, sustained correlated with a greater reduction integrated provirus. However, specific for Gag, Pol, Nef, Vif proteins positively...
Gut homing CD4+ T cells expressing the integrin α4β7 are early viral targets and contribute to HIV-1 pathogenesis, likely by seeding gastrointestinal (GI) tract with HIV. Although simianized anti-α4β7 monoclonal antibodies have shown promise in preventing or attenuating disease course of simian immunodeficiency virus nonhuman primate studies, mechanisms drug action remain elusive. We present a cohort individuals mild inflammatory bowel concomitant infection receiving treatment. By sampling...
Abstract Efforts to cure HIV have focused on reactivating latent proviruses enable elimination by CD8 + cytotoxic T-cells. Clinical studies of latency reversing agents (LRA) in antiretroviral therapy (ART)-treated individuals shown increases transcription, but without reductions virologic measures, or evidence that HIV-specific T-cells were productively engaged. Here, we show the SARS-CoV-2 mRNA vaccine BNT162b2 activates RIG-I/TLR – TNF NFκb axis, resulting transcription with minimal...
Many individuals with acute human immunodeficiency virus infection (AHI) experience retroviral syndrome (ARS), which is associated adverse long-term clinical outcomes. Participants presenting for voluntary (HIV) testing were enrolled during AHI in Bangkok, Thailand. ARS was defined by ≥3 qualifying signs/symptoms. HIV burden, immunophenotypes, and biomarkers stratified diagnosis at enrollment after up to 96 weeks of antiretroviral therapy (ART). From 212382 samples screened, 430 participants...
Estimating the size of viral reservoir is critical for HIV cure strategies. Biomarkers in peripheral circulation may give insights into establishment compartments not easily accessible. We therefore measured systemic levels 84 soluble biomarkers belonging to a broad array immune pathways acute infection both antiretroviral therapy–naive (ART-naive) individuals as well who began ART upon early detection infection. These were longitudinally during and chronic their relationship persistence was...
Background: Human IL-32 is a polyfunctional cytokine that was initially reported to inhibit HIV-1 infection. However, recent data suggest may enhance replication by activating the primary targets, CD4 + T-cells. Indeed, expressed in multiple isoforms, some of which are proinflammatory, whereas others anti-inflammatory. Setting and Methods: Here, we aimed determine relative expression isoforms test their inflammatory nature potential induce production latently infected cells from...
Abstract Severe coronavirus disease 2019 (COVID-19) is characterized by systemic inflammation and can result in protracted symptoms. Robust may trigger persistent changes hematopoietic cells innate immune memory through epigenetic mechanisms. We reveal that rare circulating stem progenitor (HSPC), enriched from human blood, match the diversity of HSPC bone marrow, enabling investigation hematopoiesis epigenomics. Following COVID-19, retain epigenomic alterations are conveyed,...
Antiretroviral (ARV) drug regimens suppress HIV-1 replication but are unable to cure infection. This leaves people living with burdened by a lifelong commitment expensive daily medication. Furthermore, it has become clear that ARV therapy does not fully restore health, leaving individuals at elevated risk for cardiovascular disease, certain types of cancers, and neurocognitive disorders, as well them exposed stigma. Efforts therefore under way develop therapies capable curing A key focus...
Significance Understanding the early events in HIV transmission will aid development of an efficacious vaccine. Productive infection requires that virions access metabolically activated CD4 + T cells. These cells are, general, limited number, which contributes to inefficient viral transmission. This report describes a mechanism whereby gp120 envelope protein can deliver activating signals activity may increase both productive mucosal tissues around time and formation reservoirs. mediates by...
HIV persists, despite immune responses and antiretroviral therapy, in viral reservoirs that seed rebound viremia if therapy is interrupted. Previously, we showed the BCL-2 protein contributes to persistence by conferring a survival advantage reservoir-harboring cells. Here, demonstrate many of family members are overexpressed HIV-infected CD4+ T cells, indicating increased tension between proapoptotic prosurvival members-and suggesting inhibition may disproportionately affect Based on these...
Gastrointestinal (GI) B cells and plasma (PCs) are critical to mucosal homeostasis the host response HIV-1 infection. Here, high-resolution mapping of human PCs sampled from colon ileum during both viremic suppressed infection identified a reduction in germinal center (GC) follicular dendritic (FDCs) viremia. Immunoglobulin A-positive (IgA
Abstract Gastrointestinal (GI) B cells and plasma (PCs) are critical to mucosal homeostasis the host response HIV-1 infection. Here, high resolution mapping of human PCs sampled from colon ileum during both viremic suppressed infection identified a reduction in germinal center (GC) follicular dendritic (FDCs) viremia. IgA + major cellular output intestinal GCs were significantly reduced PC-associated transcriptional perturbations, including type I interferon signaling, persisted...
ABSTRACT Herein, we present the first human study of anti-α4β7 therapy in a cohort HIV-1 infected subjects with mild inflammatory bowel disease. α4β7 + gut homing CD4 T cells are early viral targets and contribute to pathogenesis, likely by seeding gastrointestinal (GI) tract HIV. Although, simianized monoclonal antibodies (Mab) have shown promise preventing or attenuating disease course SIV Non-Human Primate studies, mechanisms drug action remain elusive impact on persistence remains...
Abstract Persistent HIV reservoirs in CD4⁺ T-cells pose a barrier to curing infection. We identified overexpression of enhancer zeste homolog 2 (EZH2) HIV-infected T- cells that survive cytotoxic T lymphocyte (CTL) exposure, suggesting mechanism CTL resistance. Inhibition EZH2 with the FDA-approved drug tazemetostat increased surface expression major histocompatibility complex class I (MHC-I) on T-cells, counterbalancing Nef–mediated MHC-I downregulation. This improved CTL-mediated...
Summary Cytotoxic T-lymphocytes (CTL) exert sustained pressure on reservoirs of HIV-infected cells that persist through years antiretroviral therapy (ART). This selects for latently infected cells, but also potentially express HIV possess intrinsic CTL resistance. We demonstrate such resistance exists in CD4 + T-cells survive rigorous attack and map susceptibility to cell identities states defined by single-cell multi-omics functional metabolic profiling. were prominently overrepresented...