HIV-1 activates oxidative phosphorylation in infected CD4 T cells in a human tonsil explant model
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Published:2023-05-30
Issue:
Volume:14
Page:
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ISSN:1664-3224
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Container-title:Frontiers in Immunology
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language:
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Short-container-title:Front. Immunol.
Author:
Freeman Tracey L.,Zhao Connie,Schrode Nadine,Fortune Trinisia,Shroff Sanjana,Tweel Benjamin,Beaumont Kristin G.,Swartz Talia H.
Abstract
IntroductionHuman immunodeficiency virus type 1 (HIV-1) causes a chronic, incurable infection leading to immune activation and chronic inflammation in people with HIV-1 (PWH), even with virologic suppression on antiretroviral therapy (ART). The role of lymphoid structures as reservoirs for viral latency and immune activation has been implicated in chronic inflammation mechanisms. Still, the specific transcriptomic changes induced by HIV-1 infection in different cell types within lymphoid tissue remain unexplored.MethodsIn this study, we utilized human tonsil explants from healthy human donors and infected them with HIV-1 ex vivo. We performed single-cell RNA sequencing (scRNA-seq) to analyze the cell types represented in the tissue and to investigate the impact of infection on gene expression profiles and inflammatory signaling pathways.ResultsOur analysis revealed that infected CD4+ T cells exhibited upregulation of genes associated with oxidative phosphorylation. Furthermore, macrophages exposed to the virus but uninfected showed increased expression of genes associated with the NLRP3 inflammasome pathway.DiscussionThese findings provide valuable insights into the specific transcriptomic changes induced by HIV-1 infection in different cell types within lymphoid tissue. The activation of oxidative phosphorylation in infected CD4+ T cells and the proinflammatory response in macrophages may contribute to the chronic inflammation observed in PWH despite ART. Understanding these mechanisms is crucial for developing targeted therapeutic strategies to eradicate HIV-1 infection in PWH.
Funder
National Institutes of Health
Publisher
Frontiers Media SA
Subject
Immunology,Immunology and Allergy
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