HIV Nef Promotes Expression of B-Lymphocyte Stimulator by Blood Dendritic Cells During HIV Infection in Humans

• Published in: The Journal of infectious diseases Vol. 211; no. 8; pp. 1229 - 1240
• Main Authors: Chagnon-Choquet, Josiane, Gauvin, Julie, Roger, Julien, Fontaine, Julie, Poudrier, Johanne, Roger, Michel
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15-04-2015
• Subjects: Adult; B-Cell Activating Factor - metabolism; B-Lymphocytes - metabolism; Dendritic Cells - metabolism; Female; HIV Infections - metabolism; HIV-1 - metabolism; HIV/AIDS; Human immunodeficiency virus; Humans; Male; Middle Aged; nef Gene Products, Human Immunodeficiency Virus - metabolism; STAT1 Transcription Factor - metabolism; Tretinoin - metabolism; HIV disease control versus progression; HIV Nef; dendritic cells; B lymphocyte stimulator (BLyS/BAFF)
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiu611

Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS; also known as "B-cell factor belonging to the tumor necrosis factor family" [BAFF]). We have recently shown that, in human immunodeficiency virus (HIV)-infected individuals with rapid and those with classic disease progression, B-cell dysregulations were associated with increased BLyS expression in plasma and by blood myeloid DCs (mDCs), in contrast to aviremic HIV-infected individuals with slow disease progression (also known as "elite controllers"). In previous work with transgenic mice expressing HIV genes, B-cell dysregulations were concomitant with altered mDCs and dependent on HIV negative factor (Nef). We now report that HIV Nef is detected early after infection and despite successful therapy in plasma and BLyS-overexpressing blood mDCs of HIV-infected rapid and classic progressors, whereas it is low to undetectable in aviremic slow progressors. In vitro, HIV Nef drives monocyte-derived DCs toward BLyS overexpression through a process involving STAT1. Importantly, this is counteracted in the presence of all-trans retinoic acid. Nef thus contributes to high BLyS proinflammatory profiles in HIV-infected individuals.