title: HIV-1 gp120 envelope glycoprotein determinants for cytokine burst in human monocytes.
abstract: The first step of HIV infection involves the interaction of the gp120 envelope glycoprotein to its receptor CD4, mainly expressed on CD4+ T cells. Besides its role on HIV-1 entry, the gp120 has been shown to be involved in the production of IL-1, IL-6, CCL20 and other innate response cytokines by bystander, uninfected CD4+ T cells and monocytes. However, the gp120 determinants involved in these functions are not completely understood. Whether signalling leading to cytokine production is due to CD4 or other receptors is still unclear. Enhanced chemokine receptor binding and subsequent clustering receptors may lead to cytokine production. By using a comprehensive panel of gp120 mutants, here we show that CD4 binding is mandatory for cytokine outburst in monocytes. Our data suggest that targeting monocytes in HIV-infected patients might decrease systemic inflammation and the potential tissue injury associated with the production of inflammatory cytokines. Understanding how gp120 mediates a cytokine burst in monocytes might help develop new approaches to improve the chronic inflammation that persists in these patients despite effective suppression of viremia by antiretroviral therapy.
authors.affiliation: Department of Microbiology and Immunology, and Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Benoît
authors.initials: B
authors.lastname: Levast
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Montréal, Montreal, Quebec, Canada.
authors.forename: Lucie
authors.initials: L
authors.lastname: Barblu
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Montréal, Montreal, Quebec, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Coutu
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Montréal, Montreal, Quebec, Canada.|Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Prévost
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Montréal, Montreal, Quebec, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Brassard
authors.affiliation: Department of Microbiology and Immunology, and Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Peres
authors.affiliation: Department of Microbiology and Immunology, and Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Camille
authors.initials: C
authors.lastname: Stegen
authors.affiliation: Department of Microbiology and Immunology, and Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada.|Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Madrenas
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Montréal, Montreal, Quebec, Canada.|Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.affiliation: Department of Microbiology and Immunology, and Microbiome and Disease Tolerance Centre, McGill University, Montreal, Quebec, Canada.|Centre de Recherche du Centre Hospitalier Universitaire de Montréal, Montreal, Quebec, Canada.|Department of Microbiology, Infectiology and Immunology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Andrés
authors.initials: A
authors.lastname: Finzi
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*
chemical_list: D016207:Cytokines; D015699:HIV Envelope Protein gp120