Duette, G. A. | bioRxiv Science

bioRxiv2025

The tuberculosis-associated microenvironment promotes HIV-1 persistence by impairing CD8+ T cell-mediated viral control

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is the most common coinfection in people living with HIV-1 (PLWH). This coinfection is associated with accelerated HIV-1 disease progression and reduced survival. However, the immunological and virological mechanisms driving this progression are incompletely understood. To address this knowledge gap, using pleural effusion samples from PLWH and TB, we investigated the HIV-1 genetic landscape and the anti-HIV-1 immune response impacted by a TB-associated microenvironment. Our results revealed an enrichment of genetically intact HIV-1 and impaired CD8+ T cell-mediated antiviral response at the site of HIV-1/Mtb coinfection. These findings indicate that the TB-associated microenvironment promotes the persistence of cells infected with replication-competent HIV-1 by creating a niche of reduced antiviral immune pressure, potentially contributing to the worsened clinical outcomes observed in PLWH and TB.

immunology↗

bioRxiv2023

The immunosuppressive Tuberculosis-associated microenvironment inhibits viral replication and promotes HIV-1 latency in CD4+ T cells

Author SummaryMycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is the most common coinfection among people living with HIV-1. This coinfection alters the efficacy of the immune response against both HIV-1 and Mtb, and is associated with accelerated HIV-1 disease progression and reduced survival. Enhanced HIV-1 replication in macrophages induced by Mtb coinfection may contribute to the worsened clinical outcomes observed in HIV-1/TB coinfected individuals. However, the impact of the HIV-1/TB coinfection on HIV-1 replication and latency in CD4+ T cells remains poorly studied. In this study, we used the acellular fraction of tuberculous pleural effusion (TB-PE) as a proxy for the microenvironment generated by Mtb infection. Using this physiologically relevant fluid, we investigated whether viral replication and HIV-1 latency in CD4+ T cells are affected by a TB-associated microenvironment. Interestingly, our results revealed that TB-PE shaped the transcriptional profile of CD4+ T cells impairing T cell receptor-dependent cell activation and decreased HIV-1 replication. Moreover, this immunosuppressive TB microenvironment promoted viral latency and inhibited HIV-1 reactivation in CD4+ T cells from people living with HIV-1. This study indicates that the immune response induced by TB may contribute to the persistence of the viral reservoir by silencing HIV-1 expression in individuals coinfected with both pathogens, allowing the virus to persist undetected by the immune system and increasing the size of the HIV-1 latent reservoir in cells at the site of the coinfection.

pathology↗