title: Mechanisms of downmodulation and release of tumour necrosis factor receptor induced by human immunodeficiency virus type 1 in human monocytes.
abstract: Infection of human monocytes with human immunodeficiency virus type (HIV-1 LAI) triggers the release of both the cytokine tumour necrosis factor alpha (TNF-alpha) and its soluble receptor (TNFsr). In the present study, the authors have investigated the cellular events implicated in the modulation of expression and shedding of the monocyte TNF receptor induced by HIV-1 LAI. Release of TNFsr75 was triggered at an early step of interaction of the virus particles with the monocyte, involving the envelope glycoprotein gp120. HIV-1 LAI induced an upregulation of TNFr75 mRNA, whereas TNFr55 mRNA was not detectable. TNFsr75 release required exocytosis, proteolytic cleavage by serine protease(s), but was independent of prior endocytosis of the receptor. Early shedding of TNFr75 accounted for the almost total but transient disappearance of the membrane TNF receptor P75, observed 60 min after activation with HIV-1 LAI, whereas internalization was minimal. Endogenous TNF-alpha had no role in the disappearance of its own receptor. Complete and stable restoration of TNFr expression at the cell membrane, dependent on de novo protein synthesis, occurred after 5 h, followed by massive TNFsr75 release. These results demonstrate that interaction of human monocytes with HIV-1 LAI triggers at an early stage a cascade of cellular events that lead to profound remodeling of the cell TNFr pool. Understanding the mechanisms of these receptor movements is of importance to document the central role of the TNF system in HIV infection.
authors.affiliation: INSERM U25 Hôpital Necker, Paris, France.
authors.forename: A C
authors.initials: AC
authors.lastname: Rimaniol
authors.forename: F D
authors.initials: FD
authors.lastname: Boussin
authors.forename: D
authors.initials: D
authors.lastname: Dormont
authors.forename: J F
authors.initials: JF
authors.lastname: Bach
authors.forename: F
authors.initials: F
authors.lastname: Zavala
mesh_terms: D002478:Cells, Cultured; D015536:Down-Regulation; D004705:Endocytosis / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D015497:HIV-1 / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000097:blood*; D012697:Serine Endopeptidases / Q000097:blood; D012995:Solubility
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D012697:Serine Endopeptidases