Sialoadhesin Expressed on IFN-Induced Monocytes Binds HIV-1 and Enhances Infectivity

• Published in: PloS one Vol. 3; no. 4; p. e1967
• Main Authors: Rempel, Hans, Calosing, Cyrus, Sun, Bing, Pulliam, Lynn
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.04.2008; Public Library of Science (PLoS)
• Subjects: Antigens; Antiretroviral drugs; Binding; Biological response modifiers; CD14 antigen; Cell Adhesion; Cell adhesion molecules; Cell Line; Cloning, Molecular; Comparative analysis; Cytometry; Dendritic cells; Drug therapy; Flow Cytometry; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genes; Glycoprotein gp120; Glycoproteins; Health aspects; HIV; HIV Infections - metabolism; HIV-1 - metabolism; Human immunodeficiency virus; Humans; Immune system; Immunology/Immune Response; Immunology/Innate Immunity; Immunosurveillance; Infection; Infections; Infectious Diseases/HIV Infection and AIDS; Infectivity; Inflammatory diseases; Interferon; Interferons - metabolism; Laboratories; Leukocyte migration; Lipopolysaccharide Receptors - biosynthesis; Lymphocytes; Macrophages; Medicine; Membrane Glycoproteins - biosynthesis; Models, Biological; Monocytes; Monocytes - metabolism; Neurophysiology; Permissive cells; Proteins; Receptors, Immunologic - biosynthesis; Sialic Acid Binding Ig-like Lectin 1; Tumor necrosis factor; Tumor necrosis factor-α; Veterans; Viral Load; Viremia; Virology/Immunodeficiency Viruses; Virus diseases; Viruses; United States > US; San Francisco California; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0001967

HIV-1 infection dysregulates the immune system and alters gene expression in circulating monocytes. Differential gene expression analysis of CD14(+) monocytes from subjects infected with HIV-1 revealed increased expression of sialoadhesin (Sn, CD169, Siglec 1), a cell adhesion molecule first described in a subset of macrophages activated in chronic inflammatory diseases. We analyzed sialoadhesin expression on CD14(+) monocytes by flow cytometry and found significantly higher expression in subjects with elevated viral loads compared to subjects with undetectable viral loads. In cultured CD14(+) monocytes isolated from healthy individuals, sialoadhesin expression was induced by interferon-alpha and interferon-gamma but not tumor necrosis factor-alpha. Using a stringent binding assay, sialoadhesin-expressing monocytes adsorbed HIV-1 through interaction with the sialic acid residues on the viral envelope glycoprotein gp120. Furthermore, monocytes expressing sialoadhesin facilitated HIV-1 trans infection of permissive cells, which occurred in the absence of monocyte self-infection. Increased sialoadhesin expression on CD14(+) monocytes occurred in response to HIV-1 infection with maximum expression associated with high viral load. We show that interferons induce sialoadhesin in primary CD14(+) monocytes, which is consistent with an antiviral response during viremia. Our findings suggest that circulating sialoadhesin-expressing monocytes are capable of binding HIV-1 and effectively delivering virus to target cells thereby enhancing the distribution of HIV-1. Sialoadhesin could disseminate HIV-1 to viral reservoirs during monocyte immunosurveillance or migration to sites of inflammation and then facilitate HIV-1 infection of permissive cells.