Sialoadhesin expressed on IFN-induced monocytes binds HIV-1 and enhances infectivity.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Rempel
Hans
H
Department of Laboratory Medicine at the Veterans Affairs Medical Center, San Francisco, California, United States of America.
Calosing
Cyrus
C
Sun
Bing
B
Pulliam
Lynn
L
D002448:Cell Adhesion; D002460:Cell Line; D003001:Cloning, Molecular; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D063267:Sialic Acid Binding Ig-like Lectin 1; D019562:Viral Load
D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; D007372:Interferons