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

Cronin, S.; de Vries-Egan, A.; Vahlas, Z.; Czernikier, A.; Melucci, C.; Gerber, P. P.; ONeil, T.; Gloss, B.; Sharabas, M.; Turk, G.; Verollet, C.; Balboa, L.; Palmer, S.; Duette, G. A.

doi:10.1101/2023.12.05.570223

bioRxiv · 10.1101/2023.12.05.570223

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

Cronin, S.·de Vries-Egan, A.·Vahlas, Z.·Czernikier, A.·Melucci, C.·Gerber, P. P.·ONeil, T.·Gloss, B.·Sharabas, M.·Turk, G.·Verollet, C.·Balboa, L.·Palmer, S.·Duette, G. A.

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Abstract

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.

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Cronin, S., de Vries-Egan, A., Vahlas, Z., Czernikier, A., Melucci, C., Gerber, P. P., ONeil, T., Gloss, B., Sharabas, M., Turk, G., Verollet, C., Balboa, L., Palmer, S., Duette, G. A.. 2023-12-12. The immunosuppressive Tuberculosis-associated microenvironment inhibits viral replication and promotes HIV-1 latency in CD4+ T cells. https://doi.org/10.1101/2023.12.05.570223

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