HIV Nef promotes expression of B-lymphocyte stimulator by blood dendritic cells during HIV infection in humans.
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.
Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Canada.
Josiane
J
Chagnon-Choquet
Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Canada.
Julie
J
Gauvin
Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier.
Julien
J
Roger
Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Canada.
Julie
J
Fontaine
Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Canada.
Johanne
J
Poudrier
Laboratoire d'immunogénétique, Centre de Recherche du Centre Hospitalier Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Canada.
Michel
M
Roger
D000328:Adult; D053264:B-Cell Activating Factor / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D050794:STAT1 Transcription Factor / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D053264:B-Cell Activating Factor; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D054311:nef Gene Products, Human Immunodeficiency Virus; D014212:Tretinoin
B lymphocyte stimulator (BLyS/BAFF); HIV Nef; HIV disease control versus progression; dendritic cells