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Breakthrough in HIV Research: Uncovering Dormant Infected Immune Cells
Researchers at Mount Sinai have achieved a significant advancement in the quest for an HIV cure by developing a method that reveals the hidden immune cells carrying the virus. This advancement, noted in a publication on March 6 in Nature Communications, could bring new hope to the nearly 40 million individuals living with HIV worldwide.
The human immunodeficiency virus (HIV) primarily targets the body’s immune cells, weakening the system’s ability to fend off various infections. While antiretroviral therapies can control the infection by inhibiting the virus’s propagation and preserving immune functionality, they do not eradicate the virus completely. The new technique developed by Mount Sinai’s researchers offers a promising step towards finding ways to eliminate these dormant HIV-infected cells.
Utilizing an innovative cell lineage-tracing model, the research team sought to pinpoint where HIV hides within the body’s immune system. They constructed genetic profiles for T cells—essential white blood cells responsible for immune responses—which can either harbor active or dormant HIV. The analysis of these dormant cells has revealed a new genetic pathway that could be pivotal for future therapeutic strategies.
According to Benjamin K. Chen, MD, PhD, who is a Professor of Medicine specializing in Infectious Diseases at the Icahn School of Medicine at Mount Sinai, “The primary challenge in curing HIV lies in the virus’s ability to hide within immune cells that are notoriously difficult to identify. By locating these infected cells, we can get closer to discovering methods for their elimination.”
The research team devised a genetic system to permanently mark HIV-infected cells, allowing them to investigate both the infected and dormant cell populations. They employed humanized mouse models to create a fluorescent marker that changes from red to green in response to HIV infection, retaining its visibility even during dormancy. This marking process enables the tracking of HIV-infection lineage. The team analyzed over 47,000 T cells, including those that were acutely infected, treated, or uninfected, classifying them into distinct categories such as helper T cells, memory cells, naïve cells, and subgroups within these categories. Their findings led to the identification of nine different T cell types that contained inactive HIV, along with persistent T cells that retained the virus even after prolonged antiretroviral treatment periods of 10 and 29 days.
This research opens the door to novel therapies aimed at targeting the reservoirs of dormant HIV-infected cells, potentially paving the way for a future cure. The Mount Sinai team intends to pursue further studies to test specific methods aimed at reawakening dormant HIV, with the goal of reducing the volume of infected cells.
The research received funding from various sources, including the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the Clinical and Translational Science Awards (CTSA) grant from the National Center for Advancing Translational Sciences.
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