Frontiers in immunology · 2026
NF-κB-dependent and independent inflammatory responses during acute HIV-1 infection in a model of human microglia.
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Gaete-Argel Aracelly, Ananías-Sáez Catarina, Rojas-Fuentes Cecilia, Giraldo-Ocampo Sebastian, Jara Daniela, Hernández-Díaz Tomás, Ortega-Orellana Camila, López-Palma Delia, Akiyama Hisashi, Gummuluru Suryaram, González Pablo A, Valiente-Echeverría Fernando, Soto-Rifo Ricardo
Аннотация
INTRODUCTION: Microglia are the main targets of HIV-1 infection in the central nervous system (CNS) and are considered important contributors to chronic neuroinflammation in people living with HIV (PLWH). In this study, we investigated the mechanisms leading to inflammatory responses during acute HIV-1 infection in an adult human microglia model.
METHODS: We used an adult human microglia model to characterize inflammatory responses induced by acute HIV-1 infection and analyzed publicly available datasets to assess the relationship between viral loads and cytokine levels in the cerebrospinal fluid of PLWH.
RESULTS: HIV-1 infection induced a subset of pro-inflammatory mediators, including the neurotoxic cytokines IL-6, IL-8, and IL-11, through distinct mechanisms. IL-6 and IL-8 induction depended on activation of the NF-κB signaling pathway mediated by the viral accessory protein Nef, whereas IL-11 expression relied on cellular sensing of Rev-dependent transcripts and subsequent activation of MAVS signaling. Analysis of public datasets revealed a significant correlation between viral loads and IL-6/IL-8 levels in the cerebrospinal fluid of PLWH, suggesting that active HIV-1 replication in microglia contributes to increased CNS pro-inflammatory cytokine levels even under suppressed systemic viral loads.
DISCUSSION/CONCLUSION: These findings highlight the complexity of inflammatory responses during active HIV-1 replication and provide a mechanistic framework for understanding the contribution of microglia to neuroinflammation in the CNS of PLWH.
METHODS: We used an adult human microglia model to characterize inflammatory responses induced by acute HIV-1 infection and analyzed publicly available datasets to assess the relationship between viral loads and cytokine levels in the cerebrospinal fluid of PLWH.
RESULTS: HIV-1 infection induced a subset of pro-inflammatory mediators, including the neurotoxic cytokines IL-6, IL-8, and IL-11, through distinct mechanisms. IL-6 and IL-8 induction depended on activation of the NF-κB signaling pathway mediated by the viral accessory protein Nef, whereas IL-11 expression relied on cellular sensing of Rev-dependent transcripts and subsequent activation of MAVS signaling. Analysis of public datasets revealed a significant correlation between viral loads and IL-6/IL-8 levels in the cerebrospinal fluid of PLWH, suggesting that active HIV-1 replication in microglia contributes to increased CNS pro-inflammatory cytokine levels even under suppressed systemic viral loads.
DISCUSSION/CONCLUSION: These findings highlight the complexity of inflammatory responses during active HIV-1 replication and provide a mechanistic framework for understanding the contribution of microglia to neuroinflammation in the CNS of PLWH.