TB-Associated Microenvironment Promotes HIV-1 Latency and Impairs Effector Functionality of HIV-1-Specific CD8+ T-cells

ANNEKE DE VRIES-EGAN ; ZOÏ VAHLAS ; ANTHONY L. CUNNINGHAM; LUCIANA BALBOA ; CHRISTEL VÉROLLET; SARAH PALMER; GABRIEL DUETTE

Canberra

Congreso; Australian Centre for HIV & Hepatitis (ACH2) Annual Scientific Conference 2022; 2022

Background: HIV-infected individuals are frequently co-infected with Mycobacterium tuberculosis (Mtb) - the causative agent of tuberculosis (TB) - with co-infection enhancing the infectivity of each pathogen, worsening clinical outcomes. Nevertheless, whether TB-associated microenvironments affect HIV-1 infection and latency in CD4+ T-cells, and the efficacy of CD8+ T-cells in eliminating HIV-1-infected cells, remains elusive. Therapeutically aspirated pleural effusions from TB patients (TB-PE), can reflect the microenvironment found in human respiratory cavities impacted by Mtb infection. Therefore, we investigated the effects of TB-PE on latently HIV-1-infected cells and HIV-1-specific CD8+ T-cells.Methods: Isolated CD4+ T-cells from 3 healthy donors were infected in vitro with HIV-1NL4-3 in the presence or absence of TB-PE. Viral entry was assessed through the HIV-Vpr-BlaM system, reverse transcription was quantified by qPCR, and the percentage of infection measured by p24 immunostaining. To test whether TB-PE affects HIV-1 latency reversal, CD4+ J-Lat cells were exposed to PMA with or without TB-PE and the expression of GFP measured by flow cytometry. The effector CD8+ T-cell response from 3 HIV-1-infected participants was assessed by measuring intracellular effector cytokine (IFN-γ and TNF-α) production and degranulation (CD107a/b) after stimulation with HIV-1 peptides in the presence or absence of TB-PE.Results: Our results have shown that viral entry was not affected by the presence of TB-PE. Interestingly, reverse transcription, and percentage of HIV-1 infection in primary CD4+ T-cells decreased in the presence of TB-PE (p