巨噬细胞
生物
炎症
自分泌信号
旁分泌信号
病毒复制
糖酵解
细胞生物学
离体
病毒
免疫学
体内
病毒学
体外
细胞培养
新陈代谢
受体
内分泌学
生物化学
生物技术
遗传学
作者
Fernando Real,Aiwei Zhu,Boxin Huang,Ania Belmellat,Alexis Sennepin,Thomas Vogl,Céline Ransy,M. Revol,Riccardo Arrigucci,Anne Lombès,Johannes Roth,Maria Laura Gennaro,Frédéric Bouillaud,Sarra Cristofari,Morgane Bomsel
标识
DOI:10.1038/s41467-022-33401-x
摘要
Abstract HIV-1 eradication is hindered by viral persistence in cell reservoirs, established not only in circulatory CD4 + T-cells but also in tissue-resident macrophages. The nature of macrophage reservoirs and mechanisms of persistence despite combined anti-retroviral therapy (cART) remain unclear. Using genital mucosa from cART-suppressed HIV-1-infected individuals, we evaluated the implication of macrophage immunometabolic pathways in HIV-1 persistence. We demonstrate that ex vivo, macrophage tissue reservoirs contain transcriptionally active HIV-1 and viral particles accumulated in virus-containing compartments, and harbor an inflammatory IL-1R + S100A8 + MMP7 + M4-phenotype prone to glycolysis. Reactivation of infectious virus production and release from these reservoirs in vitro are induced by the alarmin S100A8, an endogenous factor produced by M4-macrophages and implicated in “sterile” inflammation. This process metabolically depends on glycolysis. Altogether, inflammatory M4-macrophages form a major tissue reservoir of replication-competent HIV-1, which reactivate viral production upon autocrine/paracrine S100A8-mediated glycolytic stimulation. This HIV-1 persistence pathway needs to be targeted in future HIV eradication strategies.
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