The Identification of Aryl Hydrocarbon Receptor as a Novel Therapeutic Target in HIV Cure

Petronela Ancuta, PhD
Principal Investigator
University of Montreal Hospital Research Centre (CRCHUM)
Canadian HIV Cure Enterprise (CanCURE)

Professor
Department of Microbiology, Infectiology and Immunology
Université de Montréal 

This conference is hosted by Éric A. Cohen, PhD . This conference is part of the 2023-2024 IRCM conference calendar.

In person: 
IRCM Auditorium
110, avenue des Pins O, H2W 1R7 Montreal

Online:
Zoom Link : https://zoom.us/j/95269762104
ID : 952 6976 2104
Code : 476372

IRCM conferences are set to occur under a hybrid format. However, please note that last-minute changes to online-only lectures may occur due to unforeseen circumstances. We invite you to visit this webpage again a few days before attending.

About this conference

The aryl hydrocarbon receptor (AhR) regulates Th17-polarized CD4+ T cell functions, but its role in HIV-1 replication/outgrowth remains unknown. Genetic (CRISPR-Cas9) and pharmacological inhibition reveal AhR as a barrier to HIV-1 replication in T cell receptor (TCR)-activated CD4+ T cells in vitro. In single-round vesicular stomatitis virus (VSV)-G-pseudotyped HIV-1 infection, AhR blockade increases the efficacy of early/late reverse transcription and subsequently facilitated integration/translation. Moreover, AhR blockade boosts viral outgrowth in CD4+ T cells of people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Finally, RNA sequencing reveals genes/pathways downregulated by AhR blockade in CD4+ T cells of ART-treated PLWH, including HIV-1 interactors and gut-homing molecules with AhR-responsive elements in their promoters. Among them, HIC1, a repressor of Tat-mediated HIV-1 transcription and a tissue-residency master regulator, is identified by chromatin immunoprecipitation as a direct AhR target. Thus, AhR governs a T cell transcriptional program controlling viral replication/outgrowth and tissue residency/recirculation, supporting the use of AhR inhibitors in "shock and kill" HIV-1 remission/cure strategies.

About Petronela Ancuta

Dr. Petronela Ancuta has a Masters’ Degree in Medical Biology from the University of Bucharest, Romania (1992), a Diplôme d’Études Approfondies (1996) and a Ph.D. in Immunology (2000) from the Université de Paris Sud XI, Orsay, France, as well as a Diploma in Fundamental Immunology from the Pasteur Institute, Paris, France (1998). During her postdoctoral training at Harvard Medical School (2001-2006), Dr. Ancuta acquired expertise in molecular mechanisms of cell trafficking and HIV neuropathogenesis. In 2006, she was appointed Assistant Professor at the Université de Montréal and set up her research group at the CHUM Research Centre. During her career she received multiple doctoral fellowships and salary awards from ANRS, SIDACTION and INSERM, France, and FRQ-S, QC, Canada. Her Research Program is/was funded since 2006 by the ANRS, INSERM, CIHR, NIH, and GSK/NeoMed. Petronela is Full Professor in Immunology at the Université de Montréal since 2017. She is a member of the AIDS and Frontiers in Immunology Editorial boards and she serves/served as a reviewer for multiple prestigious peer review journals and funding agencies (ANRS, FRQ-S, CIHR). Her major contributions as a Principal Investigator are linked to i) the demonstration that Th17-polarized CD4+ T cells are major sites for HIV replication and viral reservoir persistence at mucosal sites during ART and ii) the identification of new HIV dependency factors in these cells that can be targeted by new drugs in an effort to decrease residual HIV transcription in ART-treated PLWH. Her group also explores how the interplay between myeloid cells and T cells in the context of gut dysbiosis fuels HIV reservoir persistence during ART. Biomedical Research in Dr Ancuta’s Laboratory creates an environment prone for the training of highly qualified personnel, as reflected by the professional success of her trainees, undergraduate/graduate students and postdoctoral fellows, in academia and industry.

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