System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Epublish

PubMed: 42666215 DOI: 10.3389/fimmu.2026.1912292

NF-κB-dependent and independent inflammatory responses during acute HIV-1 infection in a model of human microglia.

Front Immunol 17:1912292

Authors: Aracelly Gaete-Argel, Catarina Ananías-Sáez, Cecilia Rojas-Fuentes, Sebastian Giraldo-Ocampo, Daniela Jara, Tomás Hernández-Díaz, Camila Ortega-Orellana, Delia López-Palma, Hisashi Akiyama, Suryaram Gummuluru, Pablo A González, Fernando Valiente-Echeverría, Ricardo Soto-Rifo

Affiliations

  • Laboratorio de Virología Molecular y Celular, Núcleo Interdisciplinario de Microbiología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile.
  • Center for HIV/AIDS Integral Research (CHAIR), Facultad de Medicina, Universidad de Chile, Santiago, Chile.
  • Instituto Milenio en Inmunología e Inmunoterapia, Santiago, Chile.
  • Laboratorio de Virología Molecular y Celular, Núcleo Interdisciplinario de Microbiología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile. Center for HIV/AIDS Integral Research (CHAIR), Facultad de Medicina, Universidad de Chile, Santiago, Chile. Instituto Milenio en Inmunología e Inmunoterapia, Santiago, Chile.
  • Laboratorio de Virología Molecular y Celular, Núcleo Interdisciplinario de Microbiología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile. Center for HIV/AIDS Integral Research (CHAIR), Facultad de Medicina, Universidad de Chile, Santiago, Chile.
  • Laboratorio de Virología Molecular y Celular, Núcleo Interdisciplinario de Microbiología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile. Instituto Milenio en Inmunología e Inmunoterapia, Santiago, Chile.
  • Department of Virology, Immunology & Microbiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States.
  • Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

Abstract

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.

MeSH

Cytokines, Microglia, Hiv-1, Hiv, Infections