Journal Article

HIV-1 Nef Protein Affects Cytokine and Extracellular Vesicles Production in the GEN2.2 Plasmacytoid Dendritic Cell Line

Elisabetta D’Aversa, Alessandra Aiello, Roberto Gambari, Zulema Antonia Percario, Stefano Leone, Claudia Arenaccio, Flavia Giannessi, Katia Fecchi, Laurence Chaperot, Massimo Sargiacomo, Maria Carollo, Elisabetta Affabris

2021

Overview

Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset specialized in type I interferon production, whose role in Human Immunodeficiency Virus (HIV) infection and pathogenesis is complex and not yet well defined. Considering the crucial role of the accessory protein Nef in HIV pathogenicity, possible alterations in intracellular signalling and extracellular vesicle (EV) release induced by exogenous Nef on uninfected pDCs have been investigated. As an experimental model system, a human plasmacytoid dendritic cell line, GEN2.2, stimulated with a myristoylated recombinant NefSF2 protein was employed. In GEN2.2 cells, Nef treatment induced the tyrosine phosphorylation of STAT-1 and STAT-2 and the production of a set of cytokines, chemokines and growth factors including IP-10, MIP-1β, MCP-1, IL-8, TNF-α and G-CSF. The released factors differed both in type and amount from those released by macrophages treated with the same viral protein. Moreover, Nef treatment slightly reduces the production of small EVs, and the protein was found associated with the small (size < 200 nm) but not the medium/large vesicles (size > 200 nm) collected from GEN2.2 cells. These results add new information on the interactions between this virulence factor and uninfected pDCs, and may provide the basis for further studies on the interactions of Nef protein with primary pDCs.

• Publisher: MDPI AG,MDPI
• Subject: [SDV.IMM] Life Sciences [q-bio]/Immunology / Blood & organ donations / Cell Line / Chemokines / Chemokines - metabolism / Cytokines / Cytokines - metabolism / Dendritic Cells / Dendritic Cells - metabolism / Dendritic Cells - virology / Experiments / Extracellular Vesicles / Extracellular Vesicles - metabolism / Gene expression / Granulocyte colony-stimulating factor / Growth factors / HIV / HIV Infections / HIV Infections - virology / HIV-1 / HIV-1 - metabolism / HIV-1 Nef / Human immunodeficiency virus / Humans / Immune system / Immunology / Interferon / interferons / Interleukin 8 / Intracellular signalling / IP-10 protein / Kinases / Laboratories / Leukemia / Life Sciences / Macrophages / Macrophages - metabolism / Microbiology / Monocyte chemoattractant protein 1 / nef Gene Products, Human Immunodeficiency Virus / nef Gene Products, Human Immunodeficiency Virus - genetics / nef Gene Products, Human Immunodeficiency Virus - immunology / nef Gene Products, Human Immunodeficiency Virus - metabolism / Nef protein / pathogenesis / Pathogenicity / Phosphorylation / plasmacytoid dendritic cells / plasmacytoid dendritic cells; HIV-1 Nef; cytokines; extracellular vesicles / Proteins / QR1-502 / Recombinant Proteins / Signal Transduction / Stat1 protein / STAT1 Transcription Factor / STAT1 Transcription Factor - metabolism / Tumor Necrosis Factor-alpha / Tumor Necrosis Factor-alpha - metabolism / Tumor necrosis factor-α / Tyrosine / virulence / Virulence factors