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Article Dans Une Revue Nature Communications Année : 2022

S100A8-mediated metabolic adaptation controls HIV-1 persistence in macrophages in vivo

Résumé

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 M4macrophages 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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Dates et versions

hal-03810505 , version 1 (11-10-2022)

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Fernando Real, Aiwei Zhu, Boxin Huang, Ania Belmellat, Alexis Sennepin, et al.. S100A8-mediated metabolic adaptation controls HIV-1 persistence in macrophages in vivo. Nature Communications, 2022, 13, ⟨10.1038/s41467-022-33401-x⟩. ⟨hal-03810505⟩
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