title: HIV-1 and HIV-2 differentially mature plasmacytoid dendritic cells into IFN-producing cells or APCs.
abstract: HIV-1 causes a progressive impairment of immune function. HIV-2 is a naturally attenuated form of HIV, and HIV-2 patients display a slow-progressing disease. The leading hypothesis for the difference in disease phenotype between HIV-1 and HIV-2 is that more efficient T cell-mediated immunity allows for immune-mediated control of HIV-2 infection, similar to that observed in the minority of HIV-1-infected long-term nonprogressors. Understanding how HIV-1 and HIV-2 differentially influence the immune function may highlight critical mechanisms determining disease outcome. We investigated the effects of exposing primary human peripheral blood cells to HIV-1 or HIV-2 in vitro. HIV-2 induced a gene expression profile distinct from HIV-1, characterized by reduced type I IFN, despite similar upregulation of IFN-stimulated genes and viral restriction factors. HIV-2 favored plasmacytoid dendritic cell (pDC) differentiation into cells with an APC phenotype rather than IFN-α-producing cells. HIV-2, but not HIV-1, inhibited IFN-α production in response to CpG-A. The balance between pDC maturation into IFN-α-producing cells or development of an APC phenotype differentiates the early response against HIV-1 and HIV-2. We propose that divergent paths of pDC differentiation driven by HIV-1 and HIV-2 cause the observed differences in pathogenicity between the two viruses.
authors.affiliation: Immunology Section, Chelsea and Westminster Hospital, Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Imperial College, London SW10 9NH, United Kingdom;
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Royle
authors.affiliation: Retrovirus Laboratory, Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
authors.forename: David R
authors.initials: DR
authors.lastname: Graham
authors.affiliation: Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, United Kingdom; and.
authors.forename: Simone
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Division of Biological Chemistry Biocenter, Innsbruck Medical University, Innsbruck A-6020, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.affiliation: Immunology Section, Chelsea and Westminster Hospital, Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Imperial College, London SW10 9NH, United Kingdom; a.boasso@imperial.ac.uk.
authors.forename: Adriano
authors.initials: A
authors.lastname: Boasso
mesh_terms: D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D008297:Male; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D016898:Interferon-alpha